The growth in mortality rate does not flatten out at any point. The rate of death for a given cohort rises every year.
Research just published by a team of demographers at the social science research organization NORC at the University of Chicago contradicts a long-held belief that the mortality rate of Americans flattens out above age 80.
It also explains why there are only half as many people in the U.S. age 100 and above than the Census Bureau predicted there would be as recently as six years ago.
The research is based on a new way of accurately measuring mortality of Americans who are 80 years of age and older, an issue that has proven remarkably elusive in the past. The work will be significant in arriving at more accurate cost projections for programs such as Social Security and Medicare, which are based in part on mortality rates.
The research, done by Leonid A. Gavrilov and Natalia S. Gavrilova, and published in the current edition of the North American Actuarial Journal, is based on highly accurate information about the date of birth and the date of death of more than nine million Americans born between 1875 and 1895. The data is publicly available in the Social Security Administration Death Master File. "It is a remarkable resource that allowed us to build what is called an extinct birth cohort that corrects or explains a number of misunderstandings about the mortality rate of our oldest citizens," said Leonid Gavrilov.
This makes intuitive sense to me. The more things go wrong in the body the more those things cause still other things to go wrong. Plus, each component is wearing out even without the influence of failing supporting components. So why expect a flattening of the mortality curve? We won't be able to flatten or, better yet, reverse the rising mortality rate with age until we can rejuvenate. Gotta repair or replace aging parts.
Every 8 years your risk of dying doubles. That's a gruesome thought. We should fix this.
The mortality rate for people between the ages of 30 and 80 follows what is called the Gompertz Law, named for its founder, Benjamin Gompertz, who observed in 1825 that a person's risk of death in a given year doubles every eight years of age. It is a phenomenon that holds up across nations and over time and is an important part of the foundation of actuarial science.
For approximately 70 years, demographers have believed that above age 80 the Gompertz Law did not hold and that mortality rates flattened out. The work done by the Gavrilovs, a husband-and-wife team, reveals that the Gompertz Law holds at least through age 106, and probably higher, but the researchers say mortality data for those older than 106 is unreliable.
This report is yet another reminder: We need to develop rejuvenation therapies. Grow new organs. Grow stem cells of various types and inject them where needed. Develop drugs and other means to kill off senescent cells to make room for healthier cells. Develop gene therapies to repair key cells that we need to keep (e.g. brain cells that hold our memories and personalities).
Highly virtuous living key to hitting 100? Nope. Those living for a century might just have better genes.
August 3, 2011 — (Bronx, NY) — People who live to 95 or older are no more virtuous than the rest of us in terms of their diet, exercise routine or smoking and drinking habits, according to researchers at Albert Einstein College of Medicine of Yeshiva University.
Their findings, published today in the online edition of Journal of the American Geriatrics Society, suggests that "nature" (in the form of protective longevity genes) may be more important than "nurture" (lifestyle behaviors) when it comes to living an exceptionally long life. Nir Barzilai, M.D., the Ingeborg and Ira Leon Rennert Chair of Aging Research and director of the Institute for Aging Research at Einstein, was the senior author of the study.
It seems unlikely you can add decades to your life expectancy by diet and exercise. We really need gene therapies, cell therapies, cures for cancer, the ability to grow replacement organs, and other rejuvenation therapies.
At age 70 the long lived had lifestyles not much different than others at that same time of life.
Overall, people with exceptional longevity did not have healthier habits than the comparison group in terms of BMI, smoking, physical activity, or diet. For example, 27 percent of the elderly women and an equal percentage of women in the general population attempted to eat a low-calorie diet. Among long-living men, 24 percent consumed alcohol daily, compared with 22 percent of the general population. And only 43 percent of male centenarians reported engaging in regular exercise of moderate intensity, compared with 57 percent of men in the comparison group.
But just because genes protect centenarians does not mean the vast majority of us can be oblivious to our diets and lifestyles.
"Although this study demonstrates that centenarians can be obese, smoke and avoid exercise, those lifestyle habits are not good choices for most of us who do not have a family history of longevity," said Dr. Barzilai. "We should watch our weight, avoid smoking and be sure to exercise, since these activities have been shown to have great health benefits for the general population, including a longer lifespan."
You can do damage by the way you live. But aging still gradually ravages your body regardless of what choices you make.
Suppose you make it to 100 and beyond. What will kill you as you near the 114 year wall? Good chance it'll be Senile Systemic Amyloidosis (thanks Lou Pagnucco). Deposits of transthyretin protein (one of the large amyloid family of proteins) build up in the heart or other locations. Whether this is due to inflammation, an immune system gone awry, or perhaps mutations in control mechanisms for amyloid protein production remains to be discovered.
Since most of us will need assorted rejuvenation therapies (gene therapies, stem cells, replacement organs) to even reach 100 I wonder whether those of us who reach 100 by use of biotechnology will then develop Senile Systemic Amyloidosis? Or will the therapies needed to get us that far make us different enough from the natural centenarians that we won't develop amyloidosis?
Update: Seventh Day Adventists provide the evidence that diet and lifestyle really do matter.
“We reviewed eight different types of studies,” Diener said. “And the general conclusion from each type of study is that your subjective well-being – that is, feeling positive about your life, not stressed out, not depressed – contributes to both longevity and better health among healthy populations.”
A study that followed nearly 5,000 university students for more than 40 years, for example, found that those who were most pessimistic as students tended to die younger than their peers. An even longer-term study that followed 180 Catholic nuns from early adulthood to old age found that those who wrote positive autobiographies in their early 20s tended to outlive those who wrote more negative accounts of their young lives.
Of course there's the question of the direction of cause and effect. People with better health will be happier. Ditto smart people who see their way to success. A healthier and more capable body and mind has greater odds of having what it takes to go the distance.
There were a few exceptions, but most of the long-term studies the researchers reviewed found that anxiety, depression, a lack of enjoyment of daily activities and pessimism all are associated with higher rates of disease and a shorter lifespan.
Of course you might be thinking defeatist thoughts at this point: "My pessimistic outlook means I shouldn't even try to exercise and eat better since I'll die young regardless".
The message here is clear: Always Look On The Bright Side of Life .
Also, of course: Don't Worry Be Happy .
What other happy long-life songs am I missing?
A new study led by a Michigan State University business scholar suggests customer-service workers who fake smile throughout the day worsen their mood and withdraw from work, affecting productivity. But workers who smile as a result of cultivating positive thoughts – such as a tropical vacation or a child’s recital – improve their mood and withdraw less.
So think positive thoughts about a tropical island or a road trip or a night on the town.
Should you care about the rate of advance of biomedical research and biotechnology? Well, your odds of suffering from some really undesirable disorders are high enough that you really would be better off with cures for all these maladies. You odds of getting an assortment of autoimmune disorders:
The adult lifetime risk in the United States of having some kind of inflammatory autoimmune disease is 8.4 percent for women and 5.1 percent for men. Based on year 2000 population figures, that means one woman in 12 and one man in 20 will develop one of the conditions in their lifetime. The authors consider that a substantial risk and say their findings should encourage more research on the value of early diagnosis and intervention for people with increased genetic risk of arthritis. They hope the new figures will help in counseling patients and in fundraising efforts to find improved treatments.
The figures below reflect lifetime risk for the respective diseases, based on the Mayo findings.
Disease Women Men Rheumatoid Arthritis (RA) 3.6% or 1 in 28 1.7% or 1 in 59 Polymyalgia Rheumatica 2.4% 1.7% Systemic Lupus Erythematosus .9% .2% Giant Cell Arteritis 1% .5% Psoriatic Arthritis .5% .6% Primary Sjögrens syndrome .8% .04% Ankylosing Spondylitis .1% .6%
Keep in mind those are just the autoimmune disorders. Plenty of chronic kidney, liver, digestive tract, skin, neurological, and other disorders could lie in store in your future. Unfun.
The threat of future diseases makes me support better policies that increase market incentives for treatment development. For example, policy changes that could increase the returns on drug development could help you 10, 20, 30, 40 years from now.
While Japan has official life expectancies of 86.4 years for women and 79.6 years for men the number of old aged is over-counted due to a combination of poor record keeping and pension fraud.
After its survey of family registration records nationwide, the ministry found that 234,354 centenarians were listed as alive, but no one seemed to know where they were, according to the Associated Press.
So perhaps the Japanese aren't so healthy after all.
BOSTON, Mass. (Aug 9, 2010) — "Love stinks!" the J. Geils band told the world in 1980, and while you can certainly argue whether or not this tender and ineffable spirit of affection has a downside, working hard to find it does. It may even shorten your life.
A new study shows that ratios between males and females affect human longevity. Men who reach sexual maturity in a context in which they far outnumber women live, on average, three months less than men whose competition for a mate isn't as stiff. The steeper the gender ratio (also known as the operational sex ratio), the sharper the decline in lifespan.
"At first blush, a quarter of a year may not seem like much, but it is comparable to the effects of, say, taking a daily aspirin, or engaging in moderate exercise," says Nicholas Christakis, senior author on the study and professor of medicine and medical sociology at Harvard Medical School as well as professor of sociology at Harvard University's Faculty of Arts and Sciences. "A 65-year-old man is typically expected to live another 15.4 years. Removing three months from this block of time is significant."
So guys are going to suffer shorter lives in nations like China and India where female fetuses are preferentially aborted.
Send your boys to high schools that are predominately female.
First, they examined information from the Wisconsin Longitudinal Study, a long-term project involving individuals who graduated from Wisconsin high schools in 1957. The researchers calculated the gender ratios of each high-school graduating class, then ascertained how long the graduates went on to live. After adjusting for a multitude of factors, they discovered that, 50 years later, men from classes with an excess of boys did not live as long as men whose classes were gender-balanced. By one measurement, mortality for a 65-year-old who had experienced a steeper sex ratio decades earlier as a teenager was 1.6 percent higher than one who hadn't faced such stiff competition for female attention.
Next, the research team compared Medicare claims data with census data for a complete national sample of more than 7 million men throughout the United States and arrived at similar results (for technical reasons, the study was unable to evaluate results for women who outnumbered men at sexual maturity).
I wonder what the mechanism is by which life expectancy is shortened. Hormonal mechanisms that increase stress?
Short people are at greater risk of developing heart disease than tall people, according to the first systematic review and meta-analysis of all the available evidence, which is published online today (Wednesday 9 June) in the European Heart Journal .
The systematic review and meta-analysis, carried out by Finnish researchers, looked at evidence from 52 studies of over three million people and found that short adults were approximately 1.5 times more likely to develop cardiovascular heart disease and die from it than were tall people. This appeared to be true for both men and women.
My guess is the various causes of shortness (malnutrition, genetic limits on height, genetically caused diseases, toxin exposure during development, and other causes) play a big role in determining whether a short person is at increased risk. Genetic causes of shortness that do not involve diseases might not cause shorter life expectancies, or at least not to the extent that other causes of shortness do.
The 165.4 cm max for short men is 65.1 inches or 5 foot, 5 inches. The 153 cm max for short women is 60.2 inches or 5 feet tall.
From the total of 1,900 papers, the researchers selected 52 that fulfilled all their criteria for inclusion in their study. These included a total of 3,012,747 patients. On average short people were below 160.5 cms high and tall people were over 173.9 cms. When men and women were considered separately, on average short men were below 165.4 cms and short women below 153 cms, while tall men were over 177.5 cms and tall women over 166.4 cms.
Dr Paajanen and her colleagues found that compared to those in the tallest group, the people in the shortest group were nearly 1.5 times more likely to die from cardiovascular disease (CVD) or coronary heart disease (CHD), or to live with the symptoms of CVD or CHD, or to suffer a heart attack, compared with the tallest people.
Looking at men and women separately, short men were 37% more likely to die from any cause compared with tall men, and short women were 55% more likely to die from any cause compared with their taller counterparts.
A team led by Vincent Careau, a PhD student at University of Sherbrooke, gathered data on many aspects of dog biology published in disparate fields of study such as psychology, longevity, and veterinary research. The information was well known in the respective research domains, yet they were never put together. By doing so, the authors show that obedient breeds - on average - live longer than disobedient breeds. They also show that aggressive breeds have higher energy expenditure. The late Don Thomas said, "It is hard to imagine how an aggressive personality could be adaptive if it lacked the energetic and metabolic machinery to back up the threats. Simply put, 100 pound weaklings don't kick sand in weight-lifters' faces and survive in nature."
Do calm people live longer than high energy people? Anyone know of studies that compare personality traits and longevity?
Self esteem rises for years until peaking around age 60. Our bodies start decaying before our self esteem does. But eventually aging makes loss of self esteem hard to avoid.
WASHINGTON – Self-esteem rises steadily as people age but starts declining around the time of retirement, according to a longitudinal study of men and women ranging in age from 25 to 104.
"Self-esteem is related to better health, less criminal behavior, lower levels of depression and, overall, greater success in life," said the study's lead author, Ulrich Orth, PhD. "Therefore, it's important to learn more about how the average person's self-esteem changes over time."
Self-esteem was lowest among young adults but increased throughout adulthood, peaking at age 60, before it started to decline. These results are reported in the latest issue of the Journal of Personality and Social Psychology, published by the American Psychological Association.
You ascend in life until you start descending.
There are numerous theories as to why self-esteem peaks in middle age and then drops after retirement, said the researchers. "Midlife is a time of highly stable work, family and romantic relationships. People increasingly occupy positions of power and status, which might promote feelings of self-esteem," said co-author Richard Robins, PhD, of the University of California, Davis. "In contrast, older adults may be experiencing a change in roles such as an empty nest, retirement and obsolete work skills in addition to declining health."
What's the solution to this problem of declining self esteem? Cure aging. If we didn't grow old we wouldn't experience declining self esteem, declining health, declining intellectual abilities, and declining physical abilities. Full body rejuvenation is the solution. No need to retire. No chronic pain from arthritis, cartilage decay, and inflamed tissues. No disabilities, no difficulty seeing. No spontaneous fractures.
We should seek to avoid our fate as decaying, unhealthy elderly.
At age 55, men can expect another 15 years of sexual activity, but women that age should expect less than 11 years, according to a study by University of Chicago researchers published early online March 10 by the British Medical Journal. Men in good or excellent health at 55 can add 5 to 7 years to that number. Equally healthy women gain slightly less, 3 to 6 years.
One consolation for women is that many of them seem not to miss it. Men tend to marry younger women, die sooner and care more about sex, the study confirmed. Although 72 percent of men aged 75 to 85 have partners, fewer than 40 percent of women that age do. Only half of women 75-85 who remained sexually active rated their sex lives as "good," and only 11 percent of all women that age report regularly thinking about or being interested in sex. Among those age 57 to 85 not living with a partner, 57 percent of men were interested in sex, compared to only 11 percent of women.
I see this as meaning that men and women of similar age become less sexually compatible with age.
"Interest in sex, participation in sex and even the quality of sexual activity were higher for men than women, and this gender gap widened with age," said lead author Stacy Tessler Lindau, MD, associate professor of obstetrics and gynecology at the University of Chicago. But the study also "affirms a positive association between later-life health, sexual partnership and sexual activity," she said.
People who are in good health are almost twice as likely to be interested in sex compared to those in poor health, according to research published on bmj.com today.
It is already established that sexual activity has health benefits and is linked to living longer. However, this study investigates how general health impacts on the quality of sex.
Since drugs like Viagra and Cialis boost male sexual function I would expect these drugs to amplify the mismatch between aging male and aging female sexual desire.
Regular pain killer use harms your hearing? Huh, regular rain thriller ewes arms your healing?
New York, NY, March 1, 2010 – In a study published in the March 2010 issue of The American Journal of Medicine, researchers determined that regular use of aspirin, acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of hearing loss in men, particularly in younger men, below age 60.
A third of people in their 40s already suffer some hearing loss. But that rock and roll cranked up on headphones sure was good. I want periodic ear stem cell therapies so that I can listen to lots of loud music.
Hearing loss is the most common sensory disorder in the US, afflicting over 36 million people. Not only is hearing loss highly prevalent among the elderly, but approximately one third of those aged 40-49 years already suffer from hearing loss. Even mild hearing loss can compromise the ability to understand speech in the presence of background noise or multiple speakers, leading to social isolation, depression, and poorer quality of life.
Of course a study like this doesn't prove direction of causation. But apparently toxicity of aspirin to ears is already well known.
Investigators from Harvard University, Brigham and Women's Hospital, Vanderbilt University and the Massachusetts Eye and Ear Infirmary, Boston looked at factors other than age and noise that might influence the risk of hearing lose. Aspirin, acetaminophen, and ibuprofen are the 3 most commonly used drugs in the US. The ototoxic effects of aspirin are well known and the ototoxicity of NSAIDs has been suggested, but the relation between acetaminophen and hearing loss has not been examined previously. The relationship between these drugs and hearing loss is an important public health issue.
The differences in risks are substantial.
Study participants were drawn from the Health Professionals Follow-up Study, which tracked over 26,000 men every 2 years for 18 years. A questionnaire determined analgesic use, hearing loss and a variety of physiological, medical and demographic factors.
For aspirin, regular users under 50 and those aged 50-59 years were 33% more likely to have hearing loss than were nonregular users, but there was no association among men aged 60 years and older. For NSAIDs, regular users aged under 50 were 61% more likely, those aged 50-59 were 32% more likely, and those aged 60 and older were 16% more likely to develop hearing loss than nonregular users of NSAIDs.
Acetaminophen users seem to be at the most risk.
For acetaminophen, regular users aged under 50 were 99% more likely, regular users aged 50-59 were 38% more likely, and those aged 60 and older were 16% more likely to have hearing loss than nonregular users of acetaminophen.
Note that as added risk is measured here it appears to decline with age. But that's probably in part because a larger fraction of the population has hearing loss with age and so the percentage increase can't be as big. Also, these percentages do not measure severity of hearing loss which also seems likely to be higher with analgesic use.
We need the biotechnologies that will allow us to repair our broken parts. Imagine hearing and eyesight as acute and sensitive as you had when you were 12 but matched up with a mature brain that understands all that you see and hear much better.
The direction of causation is not clear but a little bit of anxiety might be good for your health. Depressed smokers must have terrible life expectancy.
A study by researchers at the University of Bergen, Norway, and the Institute of Psychiatry (IoP) at King's College London has found that depression is as much of a risk factor for mortality as smoking.
Utilising a unique link between a survey of over 60,000 people and a comprehensive mortality database, the researchers found that over the four years following the survey, the mortality risk was increased to a similar extent in people who were depressed as in people who were smokers.
Dr Robert Stewart, who led the research team at the IoP, explains the possible reasons that may underlie these surprising findings: 'Unlike smoking, we don't know how causal the association with depression is but it does suggest that more attention should be paid to this link because the association persisted after adjusting for many other factors.'
The study also shows that patients with depression face an overall increased risk of mortality, while a combination of depression and anxiety in patients lowers mortality compared with depression alone. Dr Stewart explains: 'One of the main messages from this research is that 'a little anxiety may be good for you'.
I expect people who are more prone to worry are also more prone to worry about their diet, their weight, the quality of the air they breathe, and other factors that influence their health. A worrier would be more likely to get tested for weird lumps and abnormal skin growths. A worrier would be more likely to avoid developing unhealthy habits. So I'm not surprised by these results.
In a development that could have significant ramifications for the nation's health care system, Baby Boomers may well be entering their 60s suffering far more disabilities than their counterparts did in previous generations, according to a new UCLA study. The findings, researchers say, may be due in part to changing American demographics.
Have more obesity, less exercise, and other changes in diet and lifestyle begun to cut into life expectancies?
In the study, which will be published in the January 2010 issue of the American Journal of Public Health, researchers from the division of geriatrics at the David Geffen School of Medicine at UCLA found that the cohort of individuals between the ages of 60 and 69 exhibited increases in several types of disabilities over time. By contrast, those between the ages of 70 and 79 and those aged 80 and over saw no significant increases — and in some cases exhibited fewer disabilities than their previous cohorts.
While you can hear it widely said that medicine has made great advances those advances haven't been powerful enough to prevent other factors from making people less healthy. Now, some technological trends might well accelerate the rate of advance of medical technologies so much that rejuvenation therapies and other treatments will block and reverse the effects of dietary choices and poor lifestyle choices. But that hasn't happened yet. You really do have to take care of your body. You can't count on medicine to undo the damage caused by diet and lifestyle.
Update: WebMD has a more quantitative description of how much disability is increasing for people their 60s. The rises are pretty dramatic.
Retirees who transition from full-time work into a temporary or part-time job experience fewer major diseases and are able to function better day-to-day than people who stop working altogether, according to a national study. And the findings were significant even after controlling for people’s physical and mental health before retirement.
The study's authors refer to this transition between career and complete retirement as "bridge employment," which can be a part-time job, self-employment or a temporary job. The findings are reported in the October issue of the Journal of Occupational Health Psychology, published by the American Psychological Association.
"Given the economic recession, we will probably see more people considering post-retirement employment,” said co-author Mo Wang, PhD, of the University of Maryland. “These findings highlight bridge employment's potential benefits."
What's the direction of causation? Is work therapeutic? Or do healthier people have more energy and concentration with which to keep working?
Will a baby born today live to 2109 on average? (or will AI robot terminators hunt them down and kill them?)
More than half of babies now born in the UK and other wealthy nations will live to 100 years, researchers say.
If we leave aside threats like robots, nanobots, quasars, asteroids, and VEI 8 volcanoes then I think an estimate of 100 year life expectancy is much too conservative. We are headed gaining the biotechnologies needed needed to do rejuvenation of worn out body parts. Look at the post I just did on ways to stimulate muscle stem cells to repair muscles. I expect eventual cures for cancer to enable safe restoration of youthful levels of stem cell activity and therefore much better body repair.
The leader of this study is making this prediction based on a long term trend toward longer life expectancy.
Professor Kaare Christensen, of the Danish Ageing Research Centre at the University of Southern Denmark, who led the study, said life expectancy had been increasing since 1840 and there was no sign of this trend slowing down.
The problem with this trend is that the types of advances that extend life will change with time. So far the sorts of tools used to extend life (e.g. clean water, antibiotics, vaccines, more and better foods) do not directly repair the effects of aging. But that's going to change in the lifetimes of most of the people reading this. Cures for cancer, therapies for muscle repair, and growth of replacement organs are among the treatments that'll come a lot sooner than 100 years. These therapies will extend life well beyond 100 years.
Biogerontologist Aubrey D.N.J. de Grey says we will achieve actuarial escape velocity where the rate of advance of biotechnology for repairing the body will extend life at least as fast as our bodies age. Repair rates will exceed aging rates and we will therefore effectively become younger each year. If that happens in the next 100 years (and I expect it will barring disasters that wipe out humans or destroy industrial civilization) then babies being born now will live thousands of years.
Good news for Peak Oil doomsters: The Great Depression was accompanied by a rapid rise in life expectancies. So when oil production starts declining every year and most of us lose our jobs we'll live longer?
ANN ARBOR, Mich.—The Great Depression had a silver lining: During that hard time, U.S. life expectancy actually increased by 6.2 years, according to a University of Michigan study published in the current issue of the Proceedings of the National Academy of Sciences.
Life expectancy rose from 57.1 in 1929 to 63.3 years in 1932, according to the analysis by U-M researchers José A. Tapia Granados and Ana Diez Roux. The increase occurred for both men and women, and for whites and non-whites.
"The finding is strong and counterintuitive," said Tapia Granados, the lead author of the study and a researcher at the U-M Institute for Social Research (ISR). "Most people assume that periods of high unemployment are harmful to health."
Whereas mortality declined during economic expansions.
For the study, researchers used historical life expectancy and mortality data to examine associations between economic growth and population health for 1920 to 1940. They found that while population health generally improved during the four years of the Great Depression and during recessions in 1921 and 1938, mortality increased and life expectancy declined during periods of strong economic expansion, such as 1923, 1926, 1929, and 1936-1937.
We are presented such images of poverty back in the Great Depression. From a distance one might expect unemployed people to have starved to death. But hard to square that with a rise in life expectancies. Okay, why this result?
"Working conditions are very different during expansions and recessions," Tapia Granados said. "During expansions, firms are very busy, and they typically demand a lot of effort from employees, who are required to work a lot of overtime, and to work at a fast pace. This can create stress, which is associated with more drinking and smoking.
"Also, new workers may be hired who are inexperienced, so injuries are likely to be more common. And people who are working a lot may also sleep less which is known to have implications for health. Other health-related behaviors such as diet may also change for the worse during expansions."
In recessions, Tapia Granados noted, there is less work to do, so employees can work at a slower pace. There is more time to sleep, and because people have less money, they are less likely to spend as much on alcohol and tobacco.
In addition, economic expansions are also associated with increases in atmospheric pollution which has well-documented short-term effects on cardiovascular and respiratory mortality. Other reasons that periods of economic expansion may be bad for health could include increases in social isolation and decreases in social support that typically occur when people are working more.
What I wonder: Has this pattern held up in recent years?
Workplaces have become a lot safer since the 1920s. Also, hours worked are shorter now than back then. So people working longer hours during an upturn now are probably still working less than, say, workers in the 1920s. Also, economic upturns are less associated with pollution (at least in the United States, though obviously not in China) than was the case in the 1920s and 1930s. So has economic growth become relatively safer today?
In political debates over health care the fact that the United States lags many other industrialized countries in average life expectancy is sometimes blamed on how health care is funded in the US. But John Tierney of the New York Times reports that once the lifestyles of Americans are adjusted for America's health care system comes out looking pretty good in terms of its effects on longevity.
But a prominent researcher, Samuel H. Preston, has taken a closer look at the growing body of international data, and he finds no evidence that America’s health care system is to blame for the longevity gap between it and other industrialized countries. In fact, he concludes, the American system in many ways provides superior treatment even when uninsured Americans are included in the analysis.
So why does America lag in life expectancy? Past heavy usage of the demon tobacco.
For four decades, until the mid-1980s, per-capita cigarette consumption was higher in the United States (particularly among women) than anywhere else in the developed world. Dr. Preston and other researchers have calculated that if deaths due to smoking were excluded, the United States would rise to the top half of the longevity rankings for developed countries.
I see this report as both good news and bad news. First off, Europe is now substantially lagging the United States in turning away from the demon weed. So the good news for Americans is that in future years the US life expectancy should improve faster than in some of the bigger smoking European countries like Greece, Estonia, Slovakia, Germany, and Hungary. The bad news? We do not have a big potential for longer average life expectancy via changes in funding of health care. We need to eat better food, get more exercise, and make other lifestyle changes. If you still smoke you are accelerating your aging process by about 10 years. So stop doing that!
What's going to matter most for life expectancy in the long run: The rate of advance of biomedical science and the rate of development of new drugs and other treatments. What worries me: The current debate about medical care delivery is focused on short term goals and the effects of proposed policies on long term incentives get short shrift. Yet for the vast majority of us our potentially fatal diseases lie years or decades in the future.
Researchers from the University of Chicago and Johns Hopkins' Bloomberg School of Public Health find divorced people are less healthy than married people.
Among the findings:
- Divorced or widowed people have 20 percent more chronic health conditions such as heart disease, diabetes or cancer than married people. They also have 23 percent more mobility limitations, such as trouble climbing stairs or walking a block.
- People who never married have 12 percent more mobility limitations and 13 percent more depressive symptoms, but report no difference in the number of chronic health conditions from married people.
- People who remarried have 12 percent more chronic conditions and 19 percent more mobility limitations, but no more depressive symptoms, than those who are continuously married.
The impacts of marriage, divorce and remarriage on health are based on the ways in which the various illnesses develop and heal, Waite said.
"Some health situations, like depression, seem to respond both quickly and strongly to changes in current conditions," she said. "In contrast, conditions such as diabetes and heart disease develop slowly over a substantial period and show the impact of past experiences, which is why health is undermined by divorce or widowhood, even when a person remarries."
Maybe unhealthy people are more likely to divorce. So the direction of causation is not clear.
If unhappy marriages really do worsen health then does the damage to health mostly come before the divorce? Do unhappily married people suffer as much disease as those who get divorced?
I'd like to see a longitudinal study on married people where their cortisol and other stress-related hormones are tracked. Do people with high stress get divorced more often? My guess is yes. Do the ones with low stress hormones who get divorced suffer as much of an increase in health problems from divorce as divorcees overall appear to?
Many of my readers are looking for any edge they can find to extend their lives. They are willing to embrace scientific research results that suggest that a dietary practice or lifestyle choice will help them live long enough to still be around when rejuvenation therapies hit the market. I share this desire. With this thought in mind I have a tip for the guys: Danish men who marry women much younger than them live longer.
According to the research, if a man marries a woman 15 and 17 years his junior, his chances of dying early are cut by one fifth. Also, it suggests that men cut the risk of premature death by 11 percent if their wives are seven to nine years younger.
Another aspect highlighted by the study was that men who opted for older wives have an 11 percent higher chance of dying earlier.
Now, it could be that guys who do not age as fast are more attractive in their 40s and 50s than guys who age more rapidly. So they have an advantage over more rapidly aging guys when pursuing younger women. Then they also live longer for the same reason they were able to get the young woman. But some readers might want to play it safe and marry a younger woman just on the chance this might help. Maybe she'll care for you with more energy in your old age. Or maybe you'll just find more reason to live looking at a young hottie.
The study, which covered the entire population of Denmark, tracked all deaths between 1990 and 2005.
I hear Randy Newman singing "You give me reason to live".
A study of the Utah Population Database at the University of Utah which tracks the original Mormon pioneers and their descendants finds that women who are still able to reproduce in their 40s also live longer.
SALT LAKE CITY, May 4, 2009 – Women who have babies naturally in their 40s or 50s tend to live longer than other women. Now, a new study shows their brothers also live longer, but the brothers' wives do not, suggesting the same genes prolong lifespan and female fertility, and may be more important than social and environmental factors.
"If women in your family give birth at older ages, you may well have a chance of living longer than you would otherwise," says the study's lead author, demographer Ken R. Smith, a professor of family and consumer studies at the University of Utah. "If you have a female relative who had children after age 45, then there may be some genetic benefit in your family that will enhance your longevity."
This is not a surprising result. Women whose bodies are aging more slowly are also more likely to have reproductive organs that can produce babies for a longer period of time.
Studies like this one will eventually lead to the identification of genetic variations that slow the aging process. How will we use this information? Some of us will opt to have our replacement organs grown from cells genetically modified to contain all the genetic variants that make the organs last longer.
Speaking of replacement organs, a good article in Scientific American surveys recent progress in tissue engineering and growth of replacement organs.
Women with low levels of sexual desire, often as a result of menopause, are more likely to be depressed and to suffer physical symptoms such as back pain and memory problems than women who report higher levels of desire, according to a new study by researchers at the University of North Carolina at Chapel Hill and Procter & Gamble Pharmaceuticals.
The study, published recently as an online early view article in “Value in Health,” the official journal of the International Society of Pharmacoeconomics and Outcomes Research, found that women with hypoactive sexual desire disorder (HSDD) reported poorer health status and worse health-related quality of life than women without the disorder. For example, those with the disorder were more than twice as likely to report health issues including back pain, fatigue and memory problems. Researchers say the study shows that women with the disorder have a degree of physical and mental impairment comparable to chronic conditions such as hypertension, diabetes, osteoarthritis and asthma.
What's the direction of causality here? Does a loss of sexual desire make life so much less enjoyable that everything else feels worse? Or does the same physical changes from menopause that reduce desire also increase pains? Or do women who had lower sexual desire from their teen years forward experience more rapid aging? Or does the aging of the body create the pains and also cause the decline in sexual desire? One can imagine how, for example, decreased blood flow due to cardiovascular disease could cause all these symptoms. Certainly circulatory problems contribute to impotence in some men.
Some people say that aging is graceful and full of wisdom and just another interesting stage of life full of enriching experiences. But loss of sexual desire, back pains, fatigue, and memory problems do not sound enriching to me. We need gene therapies, cell therapies, tissue engineering to grow replacement organs, nanobot repair devices, and other rejuvenating therapies to fix all these pains and losses that come with age. The sooner we get these therapies the better off we'll be.
When a smelly old diesel truck or car goes past I get annoyed at the thought that I'm briefly breathing poisonous exhaust air. When the coal electric power industry manages to delay new air pollution regulations my reaction is similar and my support for nuclear power is in part due to a desire to live longer. Well, reductions in particulate pollution probably have raised US life expectancies by 5 months in recent decades.
A new study by researchers at Brigham Young University and Harvard School of Public Health shows that average life expectancy in 51 U.S. cities increased nearly three years over recent decades, and approximately five months of that increase came thanks to cleaner air.
"Such a significant increase in life expectancy attributable to reducing air pollution is remarkable," said C. Arden Pope III, a BYU epidemiologist and lead author on the study in the Jan. 22 issue of the New England Journal of Medicine. "We find that we're getting a substantial return on our investments in improving our air quality. Not only are we getting cleaner air that improves our environment, but it is improving our public health."
The research matched two sets of data from 51 cities across the nation: changes in air pollution between about 1980 and about 2000; and residents' life expectancies during those years. The scientists applied advanced statistical models to account for other factors that could affect average life spans, such as changes in population, income, education, migration, demographics and cigarette smoking.
In cities that had previously been the most polluted and cleaned up the most, the cleaner air added approximately 10 months to the average resident's life. On average, Americans were living 2.72 years longer at the end of the two-decade study period; up to five months, or 15 percent, of that increase came because of reduced air pollution. Other studies show that these gains are likely coming from reductions in the cardiovascular and cardiopulmonary disease that typically accompany air pollution.
A reduction of 10 micrograms per cubic meter of particulate pollution will increase life expectancies by 7 months. Indoor air filtration devices anyone?
"Life expectancy is the single most comprehensive summary of how people's longevity is affected by factors like air pollution that cause early death," said co-author Majid Ezzati, associate professor of international health at Harvard School of Public Health. "We were able to use routine mortality statistics to track longevity in all cities over a long period of time and analyze how it has been influenced by changes in air pollution."
The analysis found that for every decrease of 10 micrograms per cubic meter of particulate pollution in a city, its residents' average life expectancy increased by more than seven months. During the 1980s and 1990s the average PM2.5 levels in the 51 U.S. cities studied dropped from 21 to 14 micrograms per cubic meter. In cities such as Pittsburgh and Buffalo, the decrease was closer to 14 micrograms per cubic meter.
Long commutes in crowded traffic are probably bad for your health to the exhaust particulates of older cars and trucks.
Might want to give up that fantasy of climbing Everest or K2. Very high altitude climbers appear to lose some brain mass as a result of their hobby.
A study of professional mountain climbers has shown that high-altitude exposure can cause subtle white and grey matter changes to the area of the brain involved in motor activity, according to the October issue of the European Journal of Neurology.
Italian researchers took MRI scans of nine world-class mountain climbers, who had been climbing for at least 10 years, before and after expeditions to Mount Everest (8,848 metres) and K2 (8,611 metres) without an oxygen supply. They compared their MRI brain scans with 19 age and sex matched healthy control subjects.
Both the climbers and controls were carefully checked to exclude the presence of any major systemic, psychiatric or neurological illnesses. None of the control group subjects had any history of high-altitude exposure over 3,000 metres.
The results demonstrated that the climbers showed a reduction in both the density and volume of white matter in the left pyramidal tract, near the primary and supplementary motor cortex, when their baseline measurements were compared with the control group.
And when the researchers compared the before and after scans for the climbers, they also found a reduction in the density and volume of grey matter in the left angular gyrus.
There can be costs to pushing your body beyond its limits. Oxygen starvation during high altitude ascents might inflict a cost as lost brain cells.
Climbers need a portable energy source that could concentrate oxygen from the atmosphere. People familiar with Robert Freitas's proposed artificial red blood cells called respirocytes might expect these nanodevices to some day make a walk up Everest fairly easy. But a 4 hour oxygen storage capacity for respirocytes won't take you through even one day of the hike up.
But one of the potential benefits of nanomedical devices is their ability to extend natural human capabilities. Suppose you wanted to permanently maximize the oxygen-carrying capacity of your blood by infusing the largest possible number of respirocytes. The maximum safe augmentation dosage is probably about 1 liter of 50% respirocyte suspension, which puts 954 trillion devices into your bloodstream. You could then hold your breath for 3.8 hours, at the normal resting metabolic rate. At the maximum human metabolic rate, something like a continuous Olympic-class 50-meter dash exertion level, you could go for a full 12 minutes without taking a breath. Afterwards, your entire capacity is recharged by hyperventilating for just 8 minutes - then you're ready to go again.
Maybe a nanomaterial clothing could integrate with the respirocyte system so that most of your external surface area could be harnessed for oxygen collection. Nanotech will enable more extreme sports. Picture a group of people walking across the Hudson River on the bottom of the river. Or how about a group of people walking under the length of the Golden Gate Bridge on the bottom of the inlet to the bay? Combine respirocytes with an active system for pulling oxygen out of water and humans could do a lot of underwater hiking. Long life batteries would be needed for seeing though.
You already know that cigarettes are toxic cancer sticks and increase risks of a large number of diseases. Some smokers think their habit just increases their risk of dying from one disease or another and that perhaps they'll beat the odds. But smoking speeds the aging process and makes the whole body about an additional 10 years older after years of heaving smoking.
CHICAGO—Health-related quality of life appears to deteriorate as the number of cigarettes smoked per day increases, even in individuals who subsequently quit smoking, according to a report in the October 13 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
>Smoking has been shown to shorten men’s lives between seven and 10 years, according to background information in the article. It also has been linked to factors that may reduce quality of life, including poor nutrition and lower socioeconomic status.
Arto Y. Strandberg, M.D., of the University of Helsinki, and colleagues followed 1,658 white men born between 1919 and 1934 who were healthy at their first assessment, conducted in 1974. Participants were mailed follow-up questionnaires in 2000 that assessed their current smoking status, health and quality of life. Deaths were tracked through Finnish national registers.
During the 26-year follow-up period, 372 (22.4 percent) of the men died. Those who had never smoked lived an average of 10 years longer than heavy smokers (more than 20 cigarettes per day). Non-smokers also had the best scores on all health-related quality of life measures, especially those associated with physical functioning. Physical health deteriorated at an increasing rate as the number of cigarettes smoked per day increased, with heavy smokers experiencing a decline equivalent to 10 years of aging.
"Although many smokers had quit smoking between the baseline investigation in 1974 and the follow-up examination in 2000, the effect of baseline smoking status on mortality and the quality of life in old age remained strong," the authors write. "In all, the results presented here are troubling for those who were smoking more than 20 cigarettes daily 26 years earlier; in spite of the 68.9 percent cessation rate during follow-up, 44.1 percent of the originally heavy smokers had died, and those who survived to the mean [average] age of 73 years had a significantly lower physical health-related quality of life than never-smokers."
Smokers should not fool themselves. They are going down a faster slope into old age with weakening and infirmities hitting sooner.
ATLANTA, September 3, 2008– A landmark government study suggests nearly one in two people (46%) will develop painful knee osteoarthritis over their lifetime, with the highest risk among those who are obese. According to the Arthritis Foundation, the study underscores the immediate need for the public to understand what they can do to reduce the tremendous pain, disability and cost associated with arthritis.
Arthritis is exploding in an aging population of U.S. baby boomers. Nearly one in five U.S. adults (46 million people) has arthritis and an estimated 67 million people will be affected by 2030. Osteoarthritis, the most common type of arthritis, currently affects more than 27 million people in the U.S.
Add in rheumatoid arthritis, decaying spinal disks, and other joint problems and your odds of eventually living in pain from skeletal pains become quite high. If you aren't living in pain now you probably will eventually - barring big advances in biomedical science and biotechnology.
For these and other reasons we need rejuvenation therapies. We need stem cell therapies, gene therapies, repair nanobots, better drugs, and other therapies that will undo the damage accumulating in all our bodies.
Golf can be a good investment for the health, according to a new study from the Swedish medical university Karolinska Institutet. The death rate for golfers is 40 per cent lower than for other people of the same sex, age and socioeconomic status, which correspond to a 5 year increase in life expectancy. Golfers with a low handicap are the safest.
The lower death rate by lower handicap suggests that part of the effect might flow from fitness of one's nervous system. Maybe more coordinated people live longer. Maybe the handicap gets worse faster for those whose nervous systems and muscles are aging more rapidly.
It is a well-known fact that exercise is good for the health, but the expected health gains of particular activities are still largely unknown. A team of researchers from Karolinska Institutet has now presented a study of the health effects of golf – a low-intensity form of exercise in which over 600,000 Swedes engage.
The study, which is published in Scandinavian Journal of Medicine & Science in Sports, is based on data from 300,000 Swedish golfers and shows that golf has beneficial health effects. The death rate amongst golfers is 40 per cent lower than the rest of the population, which equates to an increased life expectancy of five years.
Golfing involves walking some miles. Plus, it is a social game with groups of people discussing things as they walk around the course. A cause and effect relationship seems highly plausible.
Professor Anders Ahlbom, who has led the study with Bahman Farahmand is not surprised at the result, as he believes that there are several aspects of the game that are proved to be good for the health.
"A round of golf means being outside for four or five hours, walking at a fast pace for six to seven kilometres, something which is known to be good for the health," he says. "People play golf into old age, and there are also positive social and psychological aspects to the game that can be of help."
Getting more exercise is a good idea. Engaging in stress-lowering activities is similarly a good idea. Whether you want to play golf or not getting involved in regular stress-lowering exercise will provide real benefits.
The bigger benefit for blue collar workers is interesting. I would expect blue collar workers to get more exercise in their jobs. But they also have lower status and therefore more stress. Maybe golf relieves more stress for blue collar workers?
Golf players have a lower death rate regardless of sex, age and social group. The effect is greater for golfers from blue-collar professions than for those from white-collar professions. The lowest rates are found in the group of players with the lowest handicap (i.e. the best golfers).
Does SES control for IQ differences? Smarter people live longer. Are golfers smarter than non-golfers at the same levels of SES?
Update: In the comments "Fat Man" makes a very good point: Lots of golf courses require that you use a golf cart. So you do not get the exercise. I wonder if this is more an American phenomenon. Do Swedish golfers mostly walk their courses?
ATLANTA—May 13, 2008—A new study finds a gap in overall death rates between Americans with less than high school education and college graduates increased rapidly from 1993 to 2001. The study, which appears in the May 14 issue of PLoS ONE, says the widening gap was due to significant decreases in mortality from all causes, heart disease, cancer, stroke, and other conditions, in the most educated while death rates among the least educated remained relatively unchanged. The study is the first to examine recent trends in socioeconomic inequalities in mortality from all causes as well as several leading causes of death in the United States using national individual-level socioeconomic measures.
American Cancer Society epidemiologists led by Ahmedin Jemal, Ph.D., working with scientists from the Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS) used data from the National Vital Statistics System (NVSS) and death certificate information to analyze more than 3.5 million deaths recorded from 1993 to 2001. They found the overall death rate from all causes decreased significantly during the time period among the most educated (≥16 years) men and women, with the largest decrease in black men. In contrast, the all cause death rate actually increased in those with less than a high school education. The annual percent increase was largest among white women with less than 12 years of education (3.2 percent per year), but was also statistically significant (0.7 percent per year) in white women who had completed high school. The authors say the growing gap was caused largely by an unprecedented decrease in the all-cause death rate among the most educated men (totaling 36 percent in black men and 25 percent in white men over the nine-year interval) largely due to decreases in death rates from HIV infection, cancer, and heart disease.
We calculated annual age-standardized death rates from 1993–2001 for 25–64 year old non-Hispanic whites and blacks by level of education for all causes and for the seven most common causes of death using death certificate information from 43 states and Washington, D.C. Regression analysis was used to estimate annual percent change. The inequalities in all cause death rates between Americans with less than high school education and college graduates increased rapidly from 1993 to 2001 due to both significant decreases in mortality from all causes, heart disease, cancer, stroke, and other conditions in the most educated and lack of change or increases among the least educated. For white women, the all cause death rate increased significantly by 3.2 percent per year in the least educated and by 0.7 percent per year in high school graduates. The rate ratio (RR) comparing the least versus most educated increased from 2.9 (95% CI, 2.8–3.1) in 1993 to 4.4 (4.1–4.6) in 2001 among white men, from 2.1 (1.8–2.5) to 3.4 (2.9–3–9) in black men, and from 2.6 (2.4–2.7) to 3.8 (3.6–4.0) in white women.
Why do I make the claim that this result is due more to intelligence than to education? Linda Gottfredson and Ian Deary have demonstrated intelligence is a powerful variable for influencing longevity (PDF format).
ABSTRACT—Large epidemiological studies of almost an entire population in Scotland have found that intelligence (as measured by an IQ-type test) in childhood predicts substantial differences in adult morbidity and mortality, including deaths from cancers and cardiovascular diseases. These relations remain significant after controlling for socioeconomic variables. One possible, partial explanation of these results is that intelligence enhances individuals’ care of their own health because it represents learning, reasoning, and problem-solving skills useful in preventing chronic disease and accidental injury and in adhering to complex treatment regimens.
Also see Gottfredson's paper Intelligence: Is it the epidemiologists' elusive "fundamental cause" of social class inequalities in health? (PDF format).
My guess is that as the amount of useful knowledge available to influence longevity has increased (e.g. results from dietary and lifestyle research and new types of treatments that require patients to do much self-administration of drugs and therapies) the advantage of being smart has been amplified. If you get sick and you are smart you have more clinical trials to investigate, diets to try, and treatments to follow carefully. You are better able to understand why a treatment should benefit you and therefore more motivated to stick with it. Rather than follow the advice of one doctor you can seek out multiple experts, ask tough questions, and compare notes with other smart people chasing better treatments. You are better able to see through self-serving advice of specialists who are trying to boost their income. You are more likely to recognize serious side effects of treatments and challenge the wisdom of continued use of a treatment.
In the much longer run rejuvenation treatment delivery will become so automated and the treatments so incredibly effective that even the dumbest among us will benefit. But in the shorter run having brains and utilizing those brains to make diet, lifestyle, and other choices to maximize health can provide a big edge.
Regular daytime dozing forewarns of a significantly increased risk of stroke in older Americans, researchers reported at the American Stroke Association’s International Stroke Conference 2008.
Stroke risk was two- to four-fold greater in those with moderate dozing. This suggests that daytime dozing “may be an important and novel stroke risk factor,” said Bernadette Boden-Albala, Ph.D., lead author of the study.
In this study, dozing refers to a person unintentionally falling asleep.
Among 2,153 participants in a prospective study with an average follow-up of 2.3 years, the risk of stroke was 2.6 times greater for those classified as doing “some dozing” compared to those with “no dozing.” Those in the “significant dozing” group had a 4.5 times higher risk.
“Those are significant numbers,” said Boden-Albala, an assistant professor of neurology at Columbia University’s College of Physicians and Surgeons in New York City. “We were surprised that the impact was that high for such a short period of time.”
Sleep scientists previously have found evidence that people who experience apnea, brief periods when breathing stops during sleep, have an increased stroke risk. Research indicates that daytime sleepiness can result from sleeping poorly because of nighttime apnea.
Maybe the sleep apnea causes a sleep deficit which causes cardiovascular damage. Or maybe an oxygen deficit all night long while repeatedly going into shallow breathing modes causes the damage.
Sleep apnea is linked to all sorts of diseases you want to avoid like heart disease and cognitve decline. Of the various risk factors for sleep apnea about the only one you can do something about is obesity (unless you want to get a sex change operation into being a female).
Getting a stroke is up there with brain cancer and Alzheimer's Disease on the list of Terrible Things That Happen To Our Brains In Old Age. Together they provide a very compelling reason why we should support more rapid development of rejuvenation treatments to reverse the aging process.
You shouldn't complain to fat people about their weight. They are saving you money. A study in Plos Medicine found that obesity costs more in the short term but earlier death cuts total medical costs.
Obesity is a major cause of morbidity and mortality and is associated with high medical expenditures. It has been suggested that obesity prevention could result in cost savings. The objective of this study was to estimate the annual and lifetime medical costs attributable to obesity, to compare those to similar costs attributable to smoking, and to discuss the implications for prevention.
Methods and Findings
With a simulation model, lifetime health-care costs were estimated for a cohort of obese people aged 20 y at baseline. To assess the impact of obesity, comparisons were made with similar cohorts of smokers and “healthy-living” persons (defined as nonsmokers with a body mass index between 18.5 and 25). Except for relative risk values, all input parameters of the simulation model were based on data from The Netherlands. In sensitivity analyses the effects of epidemiologic parameters and cost definitions were assessed. Until age 56 y, annual health expenditure was highest for obese people. At older ages, smokers incurred higher costs. Because of differences in life expectancy, however, lifetime health expenditure was highest among healthy-living people and lowest for smokers. Obese individuals held an intermediate position. Alternative values of epidemiologic parameters and cost definitions did not alter these conclusions.
Although effective obesity prevention leads to a decrease in costs of obesity-related diseases, this decrease is offset by cost increases due to diseases unrelated to obesity in life-years gained. Obesity prevention may be an important and cost-effective way of improving public health, but it is not a cure for increasing health expenditures.
However, if you expect the development of artificial intelligence and/or nanobots to make manufacturing cheaper in a few decades then it makes sense to get everyone to eat less and stop smoking now. Any deferral of medical costs, even if they'll be greater in the future, will be easy to afford once the Singularity happens.
Of course, if the nanobots take over and turn hostile toward us in the Singularity (and FuturePundit does not wear Panglossian glasses) then we won't get treated for illnesses and we won't become young again. Just as the technology comes into existence that can make our bodies young again the artificial intelligences in control of that technology might just make us extinct.
Update: This study ignores one important consideration: productivity A healthier person produces more wealth. One needs to look at lifetime income earned and taxes paid along side of health care costs to come up with net economic effects. I'm expecting non-smokers to produce more than smokers because the brains of non-smokers operate less toxified. Non-smokers are going to miss fewer days of work due to illness and operate more productively while they are there. I watch the smokers taking smoking breaks. What does that cost?
Using data on 2 million people, from 80 nations, researchers from the University of Warwick and Dartmouth College in the US have found an extraordinarily consistent international pattern in depression and happiness levels that leaves us most miserable in middle age.
Their paper entitled "Is Well-being U-Shaped over the Life Cycle?" is to be published shortly in Social Science & Medicine, the world’s most-cited social science journal. The researchers found happiness levels followed a U shaped curve, with happiness higher towards the start and end of our lives and leaving us most miserable in middle age. Many previous studies of the life-course had suggested that psychological well-being stayed relatively flat and consistent as we aged.
In Britain unhappiness peaks at the same age for men and women. But in America unhappiness peaks 10 years later for men than for women. Why is that? Any guesses?
Using a sample of 1 million people from the UK, the researchers discovered that for both men and women the probability of depression peaks around 44 years of age. In the US they found a significant difference between men and women with unhappiness reaching a peak at around 40 years of age for women and 50 years of age for men.
Once full body rejuvenation becomes possible will people with youthful bodies feel happier than our current middle aged? Or will people feel compelled to stay in competition and hence feel frustrated? Maybe youthful people will spend decades and even centuries competing to get ahead with bodies and minds that are capable of allowing them to compete very intensely? Then again, maybe the robots will take over and wipe us out.
This unhappiness curve was found in a very large assortment of countries which have radically different economic conditions, customs, and laws. This suggests a biological cause rather than a social one.
They found the same U-shape in happiness levels and life satisfaction by age for 72 countries: Albania; Argentina; Australia; Azerbaijan; Belarus; Belgium; Bosnia; Brazil; Brunei; Bulgaria; Cambodia; Canada; Chile; China; Colombia; Costa Rica; Croatia; Czech Republic; Denmark; Dominican Republic; Ecuador; El Salvador; Estonia; Finland; France; Germany; Greece; Honduras; Hungary; Iceland; Iraq; Ireland; Israel; Italy; Japan; Kyrgyzstan; Laos; Latvia; Lithuania; Luxembourg; Macedonia; Malta; Mexico; Myanmar; Netherlands; Nicaragua; Nigeria; Norway; Paraguay; Peru; Philippines; Poland; Portugal; Puerto Rico; Romania; Russia; Serbia; Singapore; Slovakia; South Africa; South Korea; Spain; Sweden; Switzerland; Tanzania; Turkey; United Kingdom; Ukraine; Uruguay; USA; Uzbekistan; and Zimbabwe.
Find your country on the list?
The researchers found that some of the most obvious suspect factors were not the causes of mid-life unhappiness.
The authors, economists Professor Andrew Oswald from the University of Warwick and Professor David Blanchflower from Dartmouth College in the US, believe that the U-shaped effect stems from something inside human beings. They show that signs of mid-life depression are found in all kinds of people; it is not caused by having young children in the house, by divorce, or by changes in jobs or income.
I wonder if the mid-life unhappiness is due to the end of dreams of what is possible in youth combined with the need to struggle daily to get ahead. Then as people get older maybe they develop peace of mind about their lots in life and feel less dissatisfied about their stations in life. As brains age memory recall decreases and we lose imagination. Maybe with age a decaying ability to daydream also reduces dissatisfaction over what is as compared to what might be.
Men over age 60 who have low blood testosterone levels may be at a higher risk for fractures, according to a report in the January 14 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
One-third of all osteoporotic fractures caused by porous bones occur in men, according to background information in the article. Men with a previous osteoporotic fracture have three to four times the risk of having another fracture than a woman of the same age with a fracture. “Preventing the first such fracture may have major public health implications,” the authors note. “Thus, understanding the determinants of fracture risk in men may reduce the burden of disease through facilitating better prevention strategies.”
Christian Meier, M.D., of the University of Sydney, Concord, New South Wales, Australia, and colleagues observed 609 men (average age 72.6) between January 1989 and December 2005. The men’s bone mineral density and lifestyle factors were recorded at the beginning of the study. Serum testosterone and estradiol (an estrogen) levels were measured and the occurrence of a low-trauma fracture (associated with a fall from standing height or less) was determined during follow-up.
Low-trauma fractures occurred in 113 men during follow-up with the risk of fracture significantly higher in those with low testosterone levels. “Twenty-five men experienced multiple incident fractures,” the authors note. “A total of 149 incident fractures were reported, including 55 vertebral, 27 hip, 28 rib, six wrist and 16 upper and 17 lower extremity fractures.”
“After adjustment for sex hormone−binding globulin (a blood protein), serum testosterone and serum estradiol levels were associated with overall fracture risk,” according to the authors. “After further adjustment for major risk factors of fractures (age, weight or bone mineral density, fracture history, smoking status, calcium intake and sex hormone−binding globulin), lower testosterone was still associated with increased risk of fracture, particularly with hip and non-vertebral fractures.”
The problem with this sort of study is that it doesn't prove the direction of cause and effect. Does poorer health contribute to both lower testosterone and greater risk of bone fracture? Would supplemental testosterone reduce risk fracture? If it did then would it not increase the risk of other health problems? Hard to say. What we really need: rejuvenating cell therapies and gene therapies that will work far better than the most optimistic benefit we could hope to derive from hormone therapy.
The study, authored by James E. Gangwisch, PhD, of Columbia University in New York, explored the relationship between sleep duration and the diagnosis of diabetes over an eight-to-10-year follow-up period between 1982 and 1992 among 8,992 subjects who participated in the Epidemiologic Follow-Up Studies of the first National Health and Nutrition Examination Survey. The subjects’ ages ranged from 32 to 86 years.
According to the results, subjects who reported sleeping five or fewer hours and subjects who reported sleeping nine or more hours were significantly more likely to have incident diabetes over the follow-up period than were subjects who reported sleeping seven hours, even after adjusting for variables such as physical activity, depression, alcohol consumption, ethnicity, education, marital status, age, obesity and history of hypertension.
The effect of short sleep duration on diabetes incidence is likely to be related in part to the influence of short sleep duration upon body weight and hypertension, said Dr. Gangwisch. Experimental studies have shown sleep deprivation to decrease glucose tolerance and compromise insulin sensitivity by increasing sympathietic nervous system activity, raising evening cortisol levels and decreasing cerebral glucose utilization. The increased burden on the pancreas from insulin resistance can, over time, compromise â-cell function and lead to type two diabetes, warned Dr. Gangwisch.
Too little sleep accelerates your aging.
Knowledge about how to slow your aging only helps if you act on it. Anyone going to change their sleep habits as a result of reading this?
Harvard economist Gregory Mankiw has an interesting article in the New York Times about medical spending. Differences in life expectancies between Americans and Canadians are not due to superior medical care under a socialist system.
The differences between the neighbors are indeed significant. Life expectancy at birth is 2.6 years greater for Canadian men than for American men, and 2.3 years greater for Canadian women than American women. Infant mortality in the United States is 6.8 per 1,000 live births, versus 5.3 in Canada.
These facts are often taken as evidence for the inadequacy of the American health system. But a recent study by June and Dave O’Neill, economists at Baruch College, from which these numbers come, shows that the difference in health outcomes has more to do with broader social forces.
For example, Americans are more likely than Canadians to die by accident or by homicide. For men in their 20s, mortality rates are more than 50 percent higher in the United States than in Canada, but the O’Neills show that accidents and homicides account for most of that gap.
Mankiw points out that Americans also have a higher incidence of obesity than Canadians. This makes Americans less healthy than Canadians. Mankiw wrote his article in order to make economic arguments about health care policy. But there's also a lesson here down below the level of national policy: The odds are that you can do far more for your health by improving your diet and lifestyle than you can by getting more health care. Think about that. Sure, there are people out there who would benefit from early detection of cancer or by taking statin drugs. But you probably could do more for your health by changing your diet and getting more exercise than by getting more medical care.
To put it another way: Medical treatments today have pretty severe limits on what they can accomplish. For many diseases we have no cures. For other diseases where cures are sometimes available the treatments have success rates well below 100%. You are better off adopting diet and lifestyle practices (more vegetables, more exercise) that will reduce your odds of getting sick in the first place. There's no magical place in the world (at least not yet) where either capitalism or socialism will supply you with cure-all health care.
Autoimmune disease rheumatoid arthritis is not just painful and debilitating. Sufferers of rheumatoid arthritis are not benefiting from the rising life expectancies which the rest of the American population is experiencing.
An autoimmune inflammatory disease that takes a progressive toll on the heart, kidney and liver as well as the joints, rheumatoid arthritis (RA) is associated with a high risk of early death. This sobering fact is well known. Less is known about whether longevity has improved for RA patients over the past few decades of remarkable improvements in longevity in the general population. Are earlier diagnosis, breakthrough drugs, and more aggressive antirheumatic treatment regimens paying off in terms of survival"
Okay, so RA doesn't just tear up your joints. It attacks your internal organs. No wonder RA sufferers have shorter life expectancies. But has the advance of modern medicine since the late 1950s done anything to increase the life expectancies of RA sufferers? No.
For answers to this vital question, researchers at the Mayo Clinic conducted a sweeping comparison of mortality trends among RA subjects with those in the general population. Their unsettling results, presented in the November 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), underscore the urgent need to find strategies that will work to reduce the excess mortality consistently associated with RA.
Drawn from the comprehensive medical records of all residents of Olmsted County, Minnesota, 822 RA subjects were identified. The subjects included all residents of Rochester, Minnesota, first diagnosed with RA between January 1, 1955, and January 1, 1995, as well as all Olmsted County residents diagnosed with RA between January 1, 1995, and January 1, 2000. The subjects were 71.5 percent women, with a mean age of 57.6 years at RA incidence. All were followed up through their entire medical records until death or January 1, 2007. The median time of follow-up was 11.7 years, during which 445 of the RA subjects died.
Researchers compared the survival rates of patients diagnosed with RA in 5 time periods: 1955-1964, 1965-1974, 1975-1984, 1985-1994, and 1995-2000 using Cox regression models, adjusting for age and sex. In the 5 time periods, there was no significant difference in survival rates for RA subjects—which also means no significant gains in longevity.
Well that's bad. So what to do about it? If you don't already have rheumatoid arthritis (or other auto-immune disorders) then get more vitamin D for reduced RA risk (abstract here). Also, eat less red meat. Reduce your risks of debilitating and life shortening diseases. Eat a better diet.
BRONX, NY – People with more years of education lose their memory faster than those with less education in the years prior to a diagnosis of dementia, according to a study by researchers at Albert Einstein College of Medicine of Yeshiva University, published in the October 23rd issue of the medical journal Neurology.
The study included 117 people who developed dementia out of an original cohort of 488. The researchers, led by Charles B. Hall, Ph.D., associate professor of epidemiology and population health at Einstein, followed study participants for an average of six years using annual cognitive tests. Study participants ranged in formal education levels of less than three years of elementary school to individuals with postgraduate education.
The study found for each additional year of formal education, the rapid accelerated memory decline associated with oncoming dementia was delayed by approximately two and one half months. However, once that accelerated decline commenced, the people with more education saw their rate of cognitive decline accelerate 4 percent faster for each additional year of education. The latter portion of this finding corroborates previous research, which had shown that people with more education had more rapid memory loss after diagnosis of dementia.
Maybe the smarter people can lose more neurons before they show symptoms of decay. Then their disease is more developed when they finally start showing symptoms and by then they are on a steeper later part of the declining slope.
I really want rejuvenation therapies for my brain. I'm so not looking forward to the intellectual decline of old age. But I'm hopeful that the accelerating pace of biotechnological advance will provide solutions before most of us become demented.
Persons who are limited in their work by arthritis are considered to have arthritis-attributable work limitation (AAWL). In the United States, AAWL affects one in 20 working-age adults (aged 18--64 years) and one in three working-age adults with self-reported, doctor-diagnosed arthritis (2). To estimate state-specific prevalence of AAWL and the percentage employed among working-age U.S. adults with AAWL, CDC analyzed data from the 2003 Behavioral Risk Factor Surveillance System (BRFSS) survey. This report describes the results of that analysis, which indicated that the state-specific prevalence of AAWL among all working-age adults ranged from 3.4% (Hawaii) to 15.0% (Kentucky) (median among states: 6.7%) in 2003. Among those with self-reported, doctor-diagnosed arthritis, the prevalence of AAWL ranged from 25.1% (Nevada) to 51.3% (Kentucky) (median among states: 33.0%). In every state, persons with work limitations attributed to arthritis reported being employed less frequently than working-age adults in the state overall and persons with arthritis but not work limitations.
The percentages will rise as average age rises. Therefore the benefits of effective treatments will rise as well. Therefore we stand more to gain from developing treatments as our population ages.
Rejuvenation therapies such as gene therapies and stem cell treatments will some day slash the rate of disability caused by arthritis and could also slash disability caused by other degenerative diseases. We would each suffer less and produce more and make more money and live better lives if those therapies came sooner rather than later. I personally am convinced by the argument that we can stop and reverse aging of joints and of the rest of the body.
Researchers are questioning how much the flu vaccine prevents flu-related deaths among older people, saying it may provide less protection starting around age 70, as immune systems decline with age.
In a review article in the October issue of Lancet Infectious Diseases, researchers including Dr. Lisa Jackson, a senior investigator at the Group Health Center for Health Studies, say evidence that all older people should get flu vaccines is weak.
Read the full article for the details.
A further piece of research found that over-65s produced only half or a quarter of the antibodies to flu vaccines that younger people did. Vaccination coverage has risen steeply in the US, from 15% of the target population in 1980 to 65% today, they write. But there has been no matching drop in influenza deaths.
We need the ability to rejuvenate our immune systems. In particular we need a way to kill old immune cells that are too worn out so that healthier immune cells can take their place. Plus, we need the ability to grow replacement thymus glands. All of this will come with time. But we could get these advances sooner if we pushed harder for them.
For most of the remaining unconquered diseases we aren't going to cure them or prevent them without developing the ability to do rejuvenation on each portion of the body which malfunctions with each disease. Attempts to cure the many diseases and disorders of old age will inevitably lead to efforts to rejuvenate various malfunctioning parts of the body. Successful efforts to rejuvenate various parts of the body will lead us to the point where we can fix so many parts that full body rejuvenation becomes possible.
How will heat and cold deaths change over the coming century with global warming? Let us for the moment assume—very unrealistically—that we will not adapt at all to the future heat. Still, the biggest cross-European cold/heat study concludes that for an increase of 3.6 degrees Fahrenheit in the average European temperatures, “our data suggest that any increases in mortality due to increased temperatures would be outweighed by much larger short-term declines in cold-related mortalities.” For Britain, it is estimated a 3.6°F increase will mean 2,000 more heat deaths but 20,000 fewer cold deaths. Likewise, another paper incorporating all studies on this issue and applying them to a broad variety of settings in both developed and developing countries found that “global warming may cause a decrease in mortality rates, especially of cardiovascular diseases.”
Mind you, this benefit of warmer weather might not be found in Africa, the Middle East, the Indian subcontinent, or other already very warm places.
In industrialized countries air conditioning appears to have decreased deaths from heat.
Yet something great happened in the decades following. Death rates in Philadelphia and around the country dropped in general because of better health care. But crucially, temperatures of 100°F today cause almost no excess deaths. However, people still die more because of cold weather. One of the main reasons for the lower heat susceptibility is most likely increased access to air-conditioning. Studies seem to indicate that over time and with sufficient resources, we actually learn to adapt to higher temperatures. Consequently we will experience fewer heat deaths even when temperatures rise.
Indeed humans live longer in warmer weather and cold weather seems to wear us out more quickly if we believe a paper by Olivier Deschenes and Enrico Moretti and published by the National Bureau of Economic Research:, Extreme Weather Events, Mortality and Migration.
We estimate the effect of extreme weather on life expectancy in the US. Using high frequency mortality data, we find that both extreme heat and extreme cold result in immediate increases in mortality. However, the increase in mortality following extreme heat appears entirely driven by temporal displacement, while the increase in mortality following extreme cold is long lasting. The aggregate effect of cold on mortality is quantitatively large. We estimate that the number of annual deaths attributable to cold temperature is 27,940 or 1.3% of total deaths in the US. This effect is even larger in low income areas. Because the U.S. population has been moving from cold Northeastern states to the warmer Southwestern states, our findings have implications for understanding the causes of long-term increases in life expectancy. We calculate that every year, 5,400 deaths are delayed by changes in exposure to cold temperature induced by mobility. These longevity gains associated with long term trends in geographical mobility account for 8%-15% of the total gains in life expectancy experienced by the US population over the past 30 years. Thus mobility is an important but previously overlooked determinant of increased longevity in the United States. We also find that the probability of moving to a state that has fewer days of extreme cold is higher for the age groups that are predicted to benefit more in terms of lower mortality compared to the age groups that are predicted to benefit less.
Global warming, by decreasing exposure to cold weather, should therefore increase life expectancies of people who now live in colder climates.
I wonder whether the real benefit of a southward migration is reduced exposure to the cold or increased exposure to the rays of the sun. Greater sunlight exposure reduces depression and also increases vitamin D production and therefore reduces incidence of cancer and other diseases. But even if life expectancy benefit comes from more sunlight exposure a warming of northern climes will get people outside sooner in springtime and hence up their vitamin D production.
Cold weather also probably reduces levels of exercise. Plus, in warmer climes locally grown vegetables and fruits are available more of the year. So diets might be better in warmer areas of industrialized countries.
Some people profess to be disgusted by the sight of old men seducing young fertile women. But some biologists and anthropologists at Stanford University and UC Santa Barbara argue that the success of old men managing to impregnant younger women drove human evolution to extend human life expectancy.
Evolutionary theory predicts that senescence, a decline in survival rates with age, is the consequence of stronger selection on alleles that affect fertility or mortality earlier rather than later in life. Hamilton quantified this argument by showing that a rare mutation reducing survival is opposed by a selective force that declines with age over reproductive life. He used a female-only demographic model, predicting that female menopause at age ca. 50 yrs should be followed by a sharp increase in mortality, a “wall of death.” Human lives obviously do not display such a wall. Explanations of the evolution of lifespan beyond the age of female menopause have proven difficult to describe as explicit genetic models. Here we argue that the inclusion of males and mating patterns extends Hamilton's theory and predicts the pattern of human senescence. We analyze a general two-sex model to show that selection favors survival for as long as men reproduce. Male fertility can only result from matings with fertile females, and we present a range of data showing that males much older than 50 yrs have substantial realized fertility through matings with younger females, a pattern that was likely typical among early humans. Thus old-age male fertility provides a selective force against autosomal deleterious mutations at ages far past female menopause with no sharp upper age limit, eliminating the wall of death. Our findings illustrate the evolutionary importance of males and mating preferences, and show that one-sex demographic models are insufficient to describe the forces that shape human senescence.
Read the full research paper (free access at Plos One) for all the details.
Older Canadian men need to try harder to apply selective pressures for longer life. The brutal Amazonian Yanomamo men show this can be done.
Male fertility is nonzero till ages 55 yrs in Canada and the !Kung, 65 yrs in the Ache, 70 yrs in the Yanomamo, 60 yrs in the Tsimane, and 75 yrs in the Gambia.
So, look, you have a life expectancy that extends into the 70s or 80s because old guys managed to knock up young hot babe women. Is this upsetting? Disgusting? Reality can sometimes be that way (to quote Jello Biafra of the Dead Kennedys).
Nowadays the best ways to extend life are to develop great stem cell therapies and gene therapies. We should pursue those therapies with all the determination and gusto that old men of yesteryear (and of today) spent trying to bed young fertile women.
Update: As regular readers know, I try to look for practical ways to apply lessons I learn from reading about scientific progress. This report is no exception. I now feel obliged to knock up a beautiful woman once I reach 65 years old. I'm going to do it because I support eugenics for a longer lived human species.
I hear the Beatles singing. "All the lonely people, where do they all come from? All the lonely people, where do they all belong?" University of Chicago psychologists Louise Hawkley and John Cacioppo find that lonely people find life more stressful.
However, when the psychologists looked at the lives of the middle-aged and old people in their study, they found that although the lonely ones reported the same number of stressful life events, they identified more sources of chronic stress and recalled more childhood adversity. Moreover, they differed in how they perceived their life experiences. Even when faced with similar challenges, the lonelier people appeared more helpless and threatened. And ironically, they were less apt to actively seek help when they are stressed out.
I also hear Mr. Mackey: "Stress is bad, mmmkay?" (not that he ever said that to my knowledge)
Loneliness cranks up a stressful flight-or-flight chemical state.
Hawkley and Cacioppo then took urine samples from both the lonely and the more contented volunteers, and found that the lonely ones had more of the hormone epinephrine flowing in their bodies. Epinephrine is one of the body’s “fight or flight” chemicals, and high levels indicate that lonely people go through life in a heightened state of arousal. As with blood pressure, this physiological toll likely becomes more apparent with aging. Since the body’s stress hormones are intricately involved in fighting inflammation and infection, it appears that loneliness contributes to the wear and tear of aging through this pathway as well.
Feeling lonely? That stress ages your body more rapidly.
Lonely people don't sleep as well.
There is more bad news. When we experience the depletion caused by stress, our bodies normally rely on restorative processes like sleep to shore us up. But when the researchers monitored the younger volunteers’ sleep, they found that the lonely nights were disturbed by many “micro awakenings.” That is, they appeared to sleep as much as the normal volunteers, but their sleep was of poorer quality. Not surprisingly, the lonelier people reported more daytime dysfunction. Since sleep tends to deteriorate with age anyway, the added hit from loneliness is probably compromising this natural restoration process even more.
You can read the original paper (paid access).
Seeking an end to your loneliness seems akin to seeking a medical treatment.
I also hear Roy Orbison singing "Only The Lonely".
There goes my baby, there goes my heart
They’re gone forever, so far apart
But only the lonely know wh-y-y I cry--only the lonely
DURHAM, N.C. – Scientists examining the relationship between the intensity and length of a workout and the duration of its benefits have made a surprising discovery: More isn't necessarily better, and none may be worse than we ever imagined.
"On the surface, it seems to make sense that the harder we exercise, the better off we'll be, and by some measures that's true," says lead author Cris Slentz, Ph.D, an exercise physiologist at Duke University Medical Center. "But our studies show that a modest amount of moderately intense exercise is the best way to significantly lower the level of a key blood marker linked to higher risk of heart disease and diabetes. More intense exercise doesn't seem to do that."
What may be even more remarkable, he says, is that some of the benefits derived from a modest exercise regimen appear to last much longer than those gained from a more rigorous program.
Triglyceride lowering benefits of exercise were longer lasting for those who only exercised moderately.
The researchers found that for the most part, no amount of exercise significantly changed LDL levels. HDL levels, however, tended to improve with the length and intensity of the workout, and that the benefit was sustained over time.
But perhaps the most interesting finding was that a modest, low-intensity workout – walking just 30 minutes per day, for example, dramatically lowered triglyceride levels. Triglycerides are the particles that carry fat around in the body, and they're also a good indicator of insulin resistance, a marker for diabetes. Lowering triglyceride levels lowers risk of heart disease and diabetes.
"A proper exercise program appears to be able to lower a person's insulin resistance in just a matter of days," says Kraus. "We were also amazed to see that the lower triglyceride levels stayed low even two weeks after the workouts ended." Longer, more intense workouts didn't have nearly the same impact, they say.
People with large numbers of moles may age slower than expected, according to a study from King's. Researchers studied the skin and telomere length (a marker of biological ageing found on all cells in the body) of more than 1800 twins and found that people with a high number of moles had longer telomeres.
The 10 year study from the Twin Research Unit was funded by the Wellcome Trust and is published in the July edition of Cancer Epidemiology Biomarkers & Prevention.
The researchers compared telomere length measurements in white cells with the number of moles in more than 1800 female twins (900 pairs of twins) aged between 18 and 79 years. They found that those with high numbers of moles (greater than 100) had longer telomeres than those with very few moles (fewer than 25). The difference between the two mole groups was equivalent to six to seven years of normal ageing (estimated by looking at the average rate of telomere length loss per year in the whole group). This was not affected by other factors such as age, weight or smoking.
These results suggest those with higher numbers of moles may have a delayed ageing as they have longer telomeres and appear to keep their moles for longer. In contrast, people with shorter telomeres have lower numbers of moles and appear to lose them quicker with age - which may be a marker of accelerated ageing.
Lead researcher Dr Veronique Bataille says: ‘The results of this study are very exciting as they show, for the first time, that moley people who have a slightly increased risk of melanoma may, on the other hand, have the benefit of a reduced rate of ageing. This could imply susceptibility to fewer age-related diseases such as heart disease or osteoporosis, for example. Further studies are needed to confirm these findings.'
We need follow-up population studies to measure life expectancy for those who have more and fewer moles. But telomere is a pretty good proxy for rate of aging. On that score see my posts Chronic Stress Accelerates Aging As Measured By Telomere Length and Telomere Length Indicates Mortality Risk.
If the melanin content of moles slows down general body aging why is that? After all, most of the body is not moles. Even most of the skin is not moles. So how could the presence of moles confer much protective effect? Are the moles a proxy for more melanin inside the body?
Could we slow the rate of aging by inducing most of our cells to produce more melanin?
Jane Brody of the New York Times outlines some of the dismal details of eye aging.
How well do you see at night? If you're over 50, probably not as well as you think, no matter how many carrots you eat. The typical 50-year-old driver needs twice as much light to see as well after dark as a 30-year-old.
That is both inconvenient and dangerous. Some people are content to grow old and even try to justify the changes which happen to our bodies as the various pieces break down. But the changes to our bodies due to aging all seem like losses to me and with no compensating upside.
The tiny muscles in your irises become less able to adjust pupil sizes and so your pupils can't dilate as far and as quickly to let in more or less light as needed. As far as I'm concerned this is yet another argument for treating the development of rejuvenation therapies as an urgent matter deserving a massive research push.
In dim light or darkness, eyes adapt by widening the pupils to let in as much light as possible. The iris (the colored part of the eye surrounding the pupil) contains tiny muscles that control the size of the pupil. As you get older, these muscles (like most in the body) weaken and do not respond as well to the need to let in more light. The result is a small pupil when you try to see in poor light. It's as if your eyes were still young but you were wearing sunglasses at night.
Does the world seem darker as you get older? It literally is as far as the retinas of your eyes are concerned.
According to one account I found you start out with about 120 million rods for black/white seeing. You also start with about 6 to 7 million cones of 3 types for color sensitivity. The rods age more rapidly and hence the black/white night-time vision deteriorates so much.
There is also evidence that as we age we lose more rods than cones. In the young eye, rods outnumber cones by nine to one in the part of the retina called the macula. But an autopsy study of older adults found that while the cones remained intact, almost a third of the rods in the macula had been lost.
Plus, pigment production for rods slows as you age. Also, your lenses become more cloudy as UV light causes cross linkages to form in the lenses.
The diminished number of rods may be a factor, but in addition, the light-sensitive pigment in the rods regenerates more slowly in older eyes.
Another common change in older eyes is a gradual clouding of the lens - the formation of cataracts - which makes the lens less transparent and reduces the amount of light reaching the retina.
Some labs are working on designs of artificial replacement lenses. Also, other labs are working on ways to grow natural replacement lenses using cells and tissue engineering. One way or another we'll some day be able to replace aged lenses with lenses as young as those of a baby.
But we need much more in order to do eye rejuvenation. First off, we need cell therapies created from stem cells to send in youthful replacement muscle cells in the iris and around the eyeball. Plus, gene therapies might reinvigorate some of the aged eye muscle cells so as to avoid need for their replacement.
Aging muscles in the rest of the body also suffer from deaths of nerves that connect to them. This probably happens with eyeball muscles as well. So we might need cell therapies that grow new neurons to hook up to rejunvenated eyeball muscles.
We also need replacement cells for making rod pigments. Plus, we need cell therapies to replace lost rods and cones. Replacement rods and cones will need new nerve connections to them. Rejuvenation therapies that repair existing rods and cones would reduce the need for replacement neural connections by avoiding the loss of target rods and cones which the original eye neurons formed connections to.
We'll also need replacement cells for eye blood vessels so that the eye cells get plenty of nutrients. Creation of replacement vascular cells might also reduce the incidence of Age-related macular degeneration (AMD) diseases of the eye which involve aged arteries in the eye. On AMD Lou Pagnucco points me to a study which finds a role for excessive zinc deposits in the eye as contributors to AMD. We might also need therapies that remove built up zinc deposits.
Further on down the road we'll eventually witness the development of tissue engineering technologies so advanced that they can grow whole organ replacement parts. Replacement eyeballs will then provide much more thorough and comprehensive solutions to the problems of aging eyes. Though even if such eyeballs could be grown today we'd face the extremely difficult problem of how to hook up a replacement eyeball to all the nerves that stretch into eyes. Repairing our existing eyes might remain preferable many years due to the difficulty in connecting up new replacement eyes.
Avoiding health risk factors in midlife such as smoking, being overweight, excessive drinking and hypertension is associated with a longer and healthier life in men, according to a study in the November 15 issue of JAMA, a theme issue on men's health.
Bradley J. Willcox, M.D., of the Pacific Health Research Institute and Kuakini Medical Center in Honolulu, presented the findings of the study today at a JAMA media briefing on men's health in New York.
Persons alive at age 85 years or older are the fastest-growing age group in most industrialized countries and are among the largest consumers of health care resources. Identifying strategies for remaining healthy, vigorous, and disability-free at older ages has become a major priority, according to background information in the article. Studies with substantial numbers of long-lived participants and characteristics associated with longer survival are rare but essential to identify risk factors for health and survival at older ages.
Dr. Willcox and colleagues examined potential biological, lifestyle, and sociodemographic risk factors present at middle-age to identify risk factors for healthy survival. The study included 5,820 Japanese-American middle-aged men (average age, 54) in the Kuakini Honolulu Heart Program/Honolulu Asia Aging Study. The participants were free of illness and functional impairments and were followed for up to 40 years (1965-2005) to assess overall and exceptional survival. Exceptional survival was defined as survival to a specified age (75, 80, 85, or 90 years) without incidence of 6 major chronic diseases and without physical and cognitive impairment. The diseases were coronary heart disease, stroke, cancer (excluding nonmelanoma skin cancer), chronic obstructive pulmonary disease, Parkinson disease, and treated diabetes. Of the 5,820 original participants, 2,451 participants (42 percent) survived to age 85 years and 655 participants (11 percent) met the criteria for exceptional survival to age 85 years.
Here are the core factors you have to work on to increase your odds of reaching 85.
The researchers found that high grip strength and avoidance of overweight, hyperglycemia, hypertension, smoking, and excessive alcohol consumption were associated with both overall and exceptional survival. In addition, high education and avoidance of hypertriglyceridemia (elevated triglyceride level) were associated with exceptional survival, and lack of a marital partner was associated with death before age 85 years.
Get married, stop smoking, build muscle strength, don't drink too much alcohol, eat a diet that keeps your triglycerides down. These are all known risk factors already.
Avoid all the risk factors and your odds of reaching 85 are very high.
Risk factor models based on cumulative risk factors (survival risk score) suggest that the probability of survival to age 85 years is as high as 69 percent with no risk factors and as low as 22 percent with 6 or more risk factors. The probability of exceptional (healthy) survival to age 85 years was 55 percent with no risk factors but decreased to 9 percent with 6 or more risk factors
Rejuvenation therapies are coming. The longer you can keep yourself alive the greater the odds you'll still be around when therapies that reverse aging make it to market.
Stress can have repercussions later in life in the form of chronic fatigue, according to a new study from Karolinska Institutet. People who considered their lives to be stressful at the start of the 1970s today suffer more often from chronic fatigue than others. The study was carried out with data from the Swedish Twin registry.
Chronic fatigue is a condition characterised by long-lasting and abnormal exhaustion, often accompanied by concentration impairment, mood swings, insomnia and pain in the muscles and joints. Despite extensive research, no root causes have been identified; all that scientists know so far is that it seems to appear across all ages and social classes in many different countries.
A research group from Karolinska Institutet has now been able to show that one of the direct causes of chronic fatigue is stress. Using the results from a health survey conducted amongst almost 20,000 twins from the Swedish Twin registry in 1973 and of a repeat survey of the same population in 1998 (which contained questions about chronic fatigue), the researchers found that the group who claimed to have stressful lives 25 years previously ran a 65 per cent greater chance of developing chronic fatigue than those who did not.
The scientists also noted a correlation between emotional instability and chronic fatigue. By limiting the analysis to identical twins, the researchers were able to dismiss any causal relationship. Instead, the correlation should be interpreted as there being genetic factors that are important for both emotional instability and chronic fatigue. Using the same method, the team has been able to show that stress does actually have a direct impact on the risk of developing chronic fatigue.
Chronic stress also accelerates aging as measured by chromosome telomere length. Telomeres get shorter with age and shorten more rapidly in people who suffer from chronic stress.
Some people feel more alive and productive under pressure. But if you feel chronically under pressure you are setting yourself up to age more rapidly and get debilitating illnesses.
Some scientists theorize that gum disease contributes to the development of atherosclerosis and heart disease. Here's another piece of evidence for the argument that you really ought to floss more often.
CHICAGO -- Researchers found an increased risk of coronary heart disease for people below the age of 60 who have more than four millimeters of alveolar bone loss (the bone that holds the teeth in the mouth) from periodontal disease, according to a new study that is printed in the Journal of Periodontology.
It was found that participants with coronary heart disease had an increase of periodontal disease indicators, including alveolar bone loss, clinical attachment loss and bleeding compared to the group without coronary heart disease.
"This study is distinctive because to our knowledge, it is the first to include both the alveolar bone loss and full mouth recording of clinical attachment loss as measurements of periodontal disease," explains Dr. Karen Geismar, Department of Periodontology, School of Dentistry, Faculty of Health Science, University of Copenhagen, Denmark. "Alveolar bone loss was recently found to be the periodontal variable that had the strongest association to coronary heart disease."
The association between periodontal disease and coronary heart disease has been that chronic infections and the inflammatory response from diseases such as periodontal disease may be involved in the initiation and progression of atherosclerosis.
I'm partial to toothpicks. Flossing is too distracting.
How much do chronic infections contribute to cardiovascular disease? The answer may vary by genetic make-up. A research group has a grant to try to find genetic factors which interact with infections to influence cardiovascular disease risk.
Dr. Harald Göring, principal investigator of the new $1.9 million grant from the National Heart, Lung and Blood Institute, titled “Genetics of Infection and Its Relation to CVD Risk,” says there has not been extensive research on the role infections play in the risk for cardiovascular disease. However, a number of epidemiological studies have shown a higher-than-average prevalence of infections among people who have suffered heart attacks, strokes, and a variety of other ailments.
Some common pathogens might contribute to heart disease risk. But some people might carry genetic variations that make them immune to these common pathogens.
These pathogens include Chlamydia pneumonia, a common cause of pneumonia; Helicobacter pylori, a major cause of ulcers; Porphyromonas gingivalis, commonly associated with gum disease; hepatitis A virus, most commonly spread among school-age children and young adults; herpes simplex virus 1, the cause of cold sores; Cytomegalovirus, or human herpesvirus 5, which particularly affects the salivary glands; and human herpesvirus 8, which induces Kaposi sarcoma in persons with immunodeficiency.
“What we want to know is, since these pathogens are so common and so easily spread, how have some people managed to avoid infection?” asked Göring. “Everyone has been exposed to them, but some people don’t have antibodies for them in their bloodstream, indicating that they’ve never been infected with these pathogens and mounted an immune response. So they may have some innate resistance to infection, some other way of preventing infection in the first place. That could be due to a difference in their genetic makeup.”
In a pilot study with 600 individuals from the San Antonio Family Heart Study, Göring has already shown evidence that there are genetic variants on chromosome 21 that influence susceptibility to Chlamydia pneumonia. Now he wants to look for genetic influences on susceptibility to all seven pathogens in a larger study population.
If pathogens contribute to the development of atherosclerosis and heart disease then we can develop counters such as vaccines, antibiotics, and even gene therapies to enhance immune systems. Plus, we can brush our teeth more often.
Update: While the influence of various pathogens on cardiovascular disease risk remains to be proven the claim that fruits and vegetables lower heart disease risk is based on a much larger body of evidence.
The analysis, published in the current issue of the Journal of Nutrition (Vol. 136, pp. 2588-2593), found that the risk of coronary heart disease (CHD), conditions that cause of 20 per cent of deaths in the US and 17 per cent of deaths in Europe, was cut by four per cent for each additional fruit and vegetable portion consumed, and by seven per cent for fruit portion intake.
The link between the risk of CHD and vegetable intake however was mixed with a more beneficial relationship observed for general cardiovascular mortality (26 per cent risk reduction) than for the more specific fatal and nonfatal heart attacks (myocardial infarction) (five per cent).
I wonder why the bigger benefit from fruits. Anthocyanins?
A pair of studies in the New England Journal of Medicine find that contrary to a controversial CDC study (more on it here) released last year being overweight (which is less heavy than being obese) really does shorten life expectancy.
Being overweight during midlife is associated with an increased risk of death, according to a new study conducted by the National Cancer Institute (NCI), part of the National Institutes of Health, in collaboration with AARP, the nation's leading organization for persons 50-Plus. Results of the study appear in the August 24, 2006, issue of the New England Journal of Medicine*.
Previous research had established a link between obesity and increased risk of death, but whether a relationship also existed between being overweight and increased risk of death remained uncertain. In 2004, the Centers for Disease Control and Prevention (CDC) reported that 34.1 percent of the U.S. adult population was overweight, but not obese**. Overweight and obesity are defined using a measurement called body-mass index (BMI), calculated as a person's weight divided by the square of their height. A BMI of 18.5 - 25.0 is considered normal, whereas people who have a BMI of 25.0 - 29.9 are considered overweight, and individuals with a BMI over 30.0 are regarded as obese. (Click to view BMI chart)
The NIH-AARP Diet and Health Study of 527,265 monitored the health status of Americans from 1995 through 2005 via mailed questionnaires and by surveying death records. When the analysis focused on BMI at age 50 among persons who had never smoked, the researchers, led by Kenneth F. Adams, Ph.D., of NCI's Division of Cancer Epidemiology and Genetics, found that the risk of mortality among participants who were overweight increased by 20 to 40 percent. Mortality risk among obese participants increased two to three-fold.
"BMI at age 50 gives a more accurate representation of the amount of excess fatness a person was exposed to over decades," said Michael F. Leitzmann, M.D., NCI, senior author of the study. "On the other hand, body weight reported at age 65, for example, might reflect a recent weight loss due to cancer or other disease. If that person then dies the next year, it would be inaccurate to classify that person in the normal BMI range when their pre-cancer BMI was actually overweight."
I think their focus on BMI before major illneseses develop is the correct approach. As people get older and sicker health problems start influencing body weight and weight becomes as much an effect as a cause of health status..
They also aimed at getting data on non-smokers in order to avoid weight reduction caused by smoking.
Some earlier studies have shown that being overweight was not associated with an increased risk of death. However, smoking and chronic illness are associated with a lower BMI and an increased risk of death, which may distort the relationship between BMI and mortality.
An advantage of the current study was the availability of data on more than 186,000 male and female participants who had never smoked. This allowed the researchers to untangle the complex relationships between body weight, smoking, existing disease, and risk of death. Other possible confounding factors that were accounted for included age, race or ethnic group, level of education, physical activity, and alcohol intake.
This result is not surprising given what we know about blood lipid levels and other aspects of metabolism among the overweight and obese.
While studies have linked being either underweight or overweight to poor health, the effect of being overweight or obese on the risk of dying has been a topic of recent controversy. Researchers have long used the body-mass index (BMI), weight in kilograms divided by the square of height in meters, as a measure of the appropriateness of weight in relation to height. Researchers from Yonsei University, in Seoul, South Korea, and the Johns Hopkins Bloomberg School of Public Health report in one of the largest studies to date (over 1.2 million study participants) that having either a high or low BMI increases risk of death. The researchers found that the effect of BMI on the risk of dying varied among major causes of death and that the risk of death from being overweight or obese was greater in younger people. The study is published in the Aug. 24, 2006, edition of the New England Journal of Medicine.
While higher BMI values was associated with less respiratory causes of death the higher BMI values were associated with higher rates of cancer and heart diease. Note that cancer and heart diseases are the two biggest killers.
The researchers found that the relationship of BMI with risk of dying varied among the major causes of death considered. The risk of death from cancer increased beginning at BMI levels of 26.0-28.0 and rose further at higher levels, according to the researchers. Risk for death from respiratory causes was highest at the lowest BMI values and decreased with higher BMI values, whereas the risk of death from atherosclerotic cardiovascular disease increased progressively with higher BMI values. Information on cardiovascular risk factors showed an increasingly unfavorable profile with increasing BMI values. Study participants younger than 50 years of age had the highest relative risk of death associated with a high BMI. The researchers report no evidence of an increased risk of death for 65-year-old and above, obese individuals.
Dr. Meir Stampfer, chairman of the epidemiology department at the Harvard School of Public Health who was not involved in either study, called both articles fine.
“They show quite convincingly, yet again, that overweight and, in particular, obesity, raise the risk of mortality,’’ Dr. Stampfer said. “It really should be the final word on this issue that’s arisen as to whether overweight is actually bad for you or not.”
For overweight people losing weight and keeping it off is hard. Drugs to suppress appetite will increase life expectancy.
Men who have a low testosterone level after age 40 may have a higher risk of death over a four-year period than those with normal levels of the hormone, according to a report in the August 14/28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Unlike women undergoing menopause, middle-aged men generally do not experience a dramatic decrease in the production of sex hormones, according to background information in the article. Testosterone levels gradually decline as a man ages, decreasing approximately 1.5 percent per year after age 30. The effects of low testosterone levels include decreased muscle mass and bone density, insulin resistance, decreased sex drive, less energy, irritability and feelings of depression.
Molly M. Shores, M.D., and colleagues at the VA Puget Sound Health Care System and University of Washington, Seattle, studied the relationship between hormone levels and death in a total of 858 male veterans older than age 40 years. All participants received care in the VA Puget Sound Health Care System and had their testosterone levels checked at least twice between 1994 and 1999, with at least one week and no more than two years elapsing between tests. The men were followed for an average of 4.3 years and a maximum of eight years, through 2002.
About 19 percent (166) of the men had a low testosterone level; 28 percent (240) had an equivocal testosterone level, meaning that their tests revealed an equal number of low and normal levels; and 53 percent (452) had normal testosterone levels. One-fifth (20.1 percent) of the men with normal testosterone levels died during the course of the study, compared with 24.6 percent of men with equivocal levels and 34.9 percent of those with low levels. Men with low testosterone levels had an 88 percent increase in risk of death compared with those who had normal levels. When the researchers considered other variables that may influence risk of death, such as age, other illnesses and body mass index, the association between low testosterone levels and death persisted.
Is the lower testosterone a cause of earlier death? Or is it just another symptom of the same underlying cause? If testosterone is a cause then will testosterone supplementation increase longevity among those whose testosterone is especially low?
Those who have never married have a 58% higher risk of an earlier death, compared with a married reference group, found Robert Kaplan, Ph.D., of the University of California at Los Angeles and Richard Kronick, Ph.D., of UC San Diego.
Strikingly, the 58% never-married penalty was also higher than the 27% combined death rates for those who were separated or divorced and the 39% rate for widowed persons. they reported in the August issue of the Journal of Epidemiology and Community Health.
So if you are hesitating to enter some marriage since you think it has a high chance of failure maybe you ought to plunge in knowing that you are reducing your odds of death. On the other hand, I have a long time married friend who thinks being married makes the passage of time harder to bear.
I bet the never marrieds are less attractive than those who get married on average. Yes, there are some beautiful never-marrieds. But, again, I'm talking on average. Well, good looks are partly a measure of health.
"Having never been married may be associated with more severe isolation because it is associated with greater isolation from children and other family."
Alternatively, it might be that people who have underlying illnesses that threaten their health and shorten their life expectancy are deemed less suitable as marriage material.
Also, many of the never married men in the study died from infectious disease, most likely HIV, note the authors.
I bet a difference in average lifetime stress between the married and non-married is the biggest cause of the difference in life expectancy. Stress accelerates the aging process. Marriage could reduce stress in a number of ways. For example, I wonder if having two incomes reduces the stress of feared potential and actual unemployment.
I wonder how much of this result is due to IQ. Higher intelligence correlates with longer life expectancy and this relationship holds up even up into the genius range of IQ. Why is this relevant to marriage? Half Sigma has used the General Social Survey Wordsum test as a rough proxy for intelligence and found that the dumbest men have the lowest rates of marriage. Though the rate of never married climbs at the highest Wordsum score levels among men.
Some of the benefit from being married (at least for some married people) probably comes from having someone to pester you to see a doctor or eat better or just to assure you that you are not alone and unwanted.
The mind is a terrible thing to waste. The big risk factors for dementia are the same as the big risk factors for heart disease.
A method to predict a middle-aged person's chance of developing dementia has been devised by scientists.
The test calculates risk by assessing factors such as blood pressure level, body mass index and cholesterol levels, along with age and education.
Having any one of these risk factors doubles a person's chance of developing dementia, and having all three increases their chances by six times, said Dr. Miia Kivipelto, an associate professor at the Aging Research Centre in Stockholm, Sweden, and the study's lead author.
By assessing factors such as blood pressure, body fat and cholesterol levels in 1,400 middle-aged Finns in the 1970s and 1980s, scientists were able to predict, with a 70% accuracy rate, the onset of dementia 20 years later.
If you have high blood pressure then take blood pressure loweriing medicine. If you have high cholesterol then take a statin drug (e.g. Crestor or Lipitor). Also get more exercise and eat better food.
Gina Kolata of the New York Times has written a great article surveying the building body of evidence which shows earlier generations got classic diseases of old age sooner and did so due to infections while very young and poorer nutrition. (and I strongly urge you to read the full article)
New research from around the world has begun to reveal a picture of humans today that is so different from what it was in the past that scientists say they are startled. Over the past 100 years, says one researcher, Robert W. Fogel of the University of Chicago, humans in the industrialized world have undergone “a form of evolution that is unique not only to humankind, but unique among the 7,000 or so generations of humans who have ever inhabited the earth.”
We humans alive today are physically way different on average as compared to previous generations.
In previous centuries heart disease, lung disease, and other ailments showed up decades earlier in human lives.
The biggest surprise emerging from the new studies is that many chronic ailments like heart disease, lung disease and arthritis are occurring an average of 10 to 25 years later than they used to. There is also less disability among older people today, according to a federal study that directly measures it. And that is not just because medical treatments like cataract surgery keep people functioning. Human bodies are simply not breaking down the way they did before.
What is most interesting about these results are the suspected causes: events in the womb and while still quite young can set people up for chronic diseases decades later.
The proposed reasons are as unexpected as the changes themselves. Improved medical care is only part of the explanation; studies suggest that the effects seem to have been set in motion by events early in life, even in the womb, that show up in middle and old age.
“What happens before the age of 2 has a permanent, lasting effect on your health, and that includes aging,” said Dr. David J. P. Barker, a professor of medicine at Oregon Health and Science University in Portland and a professor of epidemiology at the University of Southampton in England.
But it is too late for us to go back in time and tell our mothers to avoid people with colds and flus and other infectious diseases. Our bodies are damaged even from before birth. To fix that damage we need gene therapy, stem cells, and the rest of the panoply of coming rejuvenation therapies.
We are taller, heavier, live longer, get sick later. Almost half of 65 year olds can expect to reach 85. I want that percentage to rise much higher.
In 1900, 13 percent of people who were 65 could expect to see 85. Now, nearly half of 65-year-olds can expect to live that long.
People even look different today. American men, for example, are nearly 3 inches taller than they were 100 years ago and about 50 pounds heavier.
One factor that is different today is that we get infected less and suffer from infections for shorter periods of time. Improved hygiene (e.g. refrigerators and a variety of methods of killing and avoiding food borne pathogens), vaccines, antibiotics, better nutrition, and less exposure to extremes of weather all reduce our rates of infectious disease.
Even if one does not die while infected the infectious diseases take their toll and accelerate aging in a number of ways. First off, the pathogens directly do damage to the body. Second, the immune system's response does damage. In the process of attacking pathogens the immune response causes collateral damage to human tissue. Chemical compounds released by immune cells do damage to our own cells. Third, infection reduces our ability to stay nourished due to decreased appetite, diarrhea, decreased ability to do activities that bring in food, and other mechanisms. Therefore a reduction in infectious disease exposure has reduced the rate at which our bodies accumulate damage.
Conventional wisdom has it that people live longer today because when they do get sick medical treatments can keep them alive. But Dr. Fogel's study of US Civil War veteran medical records shows that back then people got serious illnesses at much younger ages, decades sooner. They lived with these illnesses for much of their lives.
Instead of inferring health from causes of death on death certificates, Dr. Fogel and his colleagues looked at health throughout life. They used the daily military history of each regiment in which each veteran served, which showed who was sick and for how long; census manuscripts; public health records; pension records; doctors’ certificates showing the results of periodic examinations of the pensioners; and death certificates.
They discovered that almost everyone of the Civil War generation was plagued by life-sapping illnesses, suffering for decades. And these were not some unusual subset of American men — 65 percent of the male population ages 18 to 25 signed up to serve in the Union Army. “They presumably thought they were fit enough to serve,” Dr. Fogel said.
Suddenly travel to the past in a time machine has gotten a lot less attractive. Even if one could go back with even more vaccines than we have today the environment back then would take a heavy toll. Though if you could go back and get rich and choose a less severe environment you could buffer yourself from some of the ravages of previous eras.
Note that people living back in the 1800s ate what today would be considered a much more natural diet. No pesticides. No trans fatty acids on french fries. But they had a much higher incidence of heart disease.
Eighty percent had heart disease by the time they were 60, compared with less than 50 percent today. By ages 65 to 74, 55 percent of the Union Army veterans had back problems. The comparable figure today is 35 percent.
That higher rate of heart disease could at least in part be due to chronic infections.
Economist Douglas V. Almond at Columbia University examined health records of children born around the time of the great killer 1918 influenza pandemic and found that women were pregnant during the pandemic gave birth to children who fared much worse by several measures as compared to children born right before or after the pandemic.
To his astonishment, Dr. Almond found that the children of women who were pregnant during the influenza epidemic had more illness, especially diabetes, for which the incidence was 20 percent higher by age 61. They also got less education — they were 15 percent less likely to graduate from high school. The men’s incomes were 5 percent to 7 percent lower, and the families were more likely to receive public assistance.
The effects, Dr. Almond said, occurred in whites and nonwhites, in rich and poor, in men and women. He convinced himself, he said, that there was something to the Barker hypothesis.
Pet peeve: I think employers should organize workplaces to reduce the incidence of diseases transmission at work. Discourage sick people from working. I hate hearing people coughing over the cubicle walls and then seeing other people getting sick. Not only does this cost economically but it is probably also shortening our lifespans. Workplace doors, bathrooms, kitchens, and other locations could be reworked to reduce touching of common surfaces.
You wash your hands in the lavatory sink but have to turn the turn the faucet handle to turn off the water (how about foot pedals?) and then turn a door handle to get out of the room. Low cubicle walls also allow cough droplets to travel across a room. In workplaces where employers push wellness programs on employees shouldn't the employers put more effort into reducing our odds of getting sick while at work?
These results go a long way toward confirming the arguments of evolutionary theorists Gregory Cochran and Paul Ewald that the role of infections in causing chronic illnesses has been much underestimated.
People who live alone double their risk of serious heart disease as those who live with a partner, suggests research in the Journal of Epidemiology and Community Health. This includes severe angina and heart attack.
The finding is based on a study of more than 138,000 adults between the ages of 30 and 69 living in one area (Aarhus) of Denmark.
Between 2000 and 2002, 646 people were diagnosed with severe angina, or sustained a heart attack, or sudden cardiac death, a spectrum of conditions known as acute coronary syndrome.
When analysed in detail, using information from population registers, poor educational attainment and living on a pension were associated with an increased risk of the syndrome.
But the two strongest predictive factors for the syndrome were age and living alone.
Women above the age of 60 and living by themselves, and men over the age of 50, in the same position, were twice as likely to have the syndrome as everyone else.
Lone women over 60 comprised just over 5 per cent, and lone men over 50 just under 8 per cent, of the whole population.
Yet lone women in this age group accounted for a third of all deaths from the syndrome within 30 days of diagnosis, while lone men in this age group accounted for two thirds of deaths.
The lowest risks included cohabiting with a partner, a high level of education, and being in work. Women divorcees also enjoyed a lower risk of the syndrome.
The authors say that certain risk factors tend to be more common in the lifestyles of those who live by themselves, which may help to explain the differences.
These include smoking, obesity, high cholesterol and fewer visits to the family doctor. People living on their own may be less able to draw on social support networks as well, say the authors.
Keep working and try to stay hooked up.
ARLINGTON HEIGHTS, Ill. – Want to know a person's real age? Just look at their hands, reports a study in the June issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). According to the study, most people can accurately tell a person's age by viewing only their hands.
"A primary motivation to have plastic surgery is to look and feel better, often by seeking a younger looking appearance. However, looking younger after your facelift or eyelid surgery can conflict with aged hands that simply do not match the face," said Roxanne Guy, MD, ASPS president-elect. "After the face, hands are the second most visible, tell-tale sign of one's age. If your goal is to look more youthful or you are bothered by the appearance of your hands, you may seriously want to consider hand rejuvenation."
In the study, people examined unaltered photographs of female hands and were asked to estimate the women's ages, i.e., younger than 20 years, 20 to 30 years, 30 to 40 years, etc. In the majority of cases, participants were able to accurately estimate the age of each woman in the unaltered photographs.
Participants were also asked to compare digitally altered photographs of female hands – blemishes and hand veins were removed or jewelry and nail polish were added – to unaltered photographs to assess which hands looked younger. The majority of participants felt that the altered photos of women's hands appeared younger. However, alterations to photos of very elderly hands – characterized by thin skin, age spots, wrinkles, deformity, veins and prominent joints – did not change the participants' ability to distinguish the person's age.
Overall, the physical characteristic which most commonly gave away age was prominent hand veins.
This being a press release from a society of plastic surgeons they went on to explain how plastic surgeons can do many things to hands to make them look younger. But SENS therapies that make our bodies younger through and through would be far more appealing.
Do people who have younger looking hands live longer on average? Does the outwardly visible condition of one's hands serve as a pretty good proxy for one's general rate of aging?
I'm expecting rejuvenation for skin to come much sooner than rejuvenation for some other parts of the body. The skin is very accessible for delivering treatments whether those treatments be gene therapies, cell therapies, or drugs that break age-related crosslinks between cells and fibers. Plus, people are willing to take risks in order to look better. Also, people spend their own money on plastic surgery rather than insurance money and are willing to pay for experimental treatments that will make them look better.
A RAND Corporation study finds that middle-aged people in the United States are sicker than middle-aged people in England.
Middle-aged Americans are less healthy than their English counterparts, according to a study issued today by researchers from the RAND Corporation, University College London and the Institute for Fiscal Studies in London.
Analyzing surveys of large groups of middle-aged people from the United States and England, researchers found that Americans ages 55 to 64 suffer from diseases such as diabetes, high-blood pressure and lung cancer at rates up to twice those seen among similar aged people in England.
The prevalence of diabetes was twice as high in the United States (12.5 percent) as compared to England (6.1 percent), while high blood pressure was about 10 percentage points higher in the United States than in England. Heart disease was 50 percent more common among middle-aged Americans than the English, while the rates of stroke, lung disease and cancer were higher among Americans as well.
The differences were confirmed when researchers analyzed separate studies that collected blood samples from participants to look for biological markers of disease. This showed that the differences were not just a result of Americans' increased willingness to report illness.
The study appears in the May 3 edition of the Journal of the American Medical Association.
“You don't expect the health of middle-aged people in these two countries to be too different, but we found that the Americans are a lot less healthy than the English,” said James P. Smith, a RAND economist and one of the study's authors. “It's not just a difference in how people characterize their own health. The biological measures confirm there is a difference.”
Reports of poorer health were seen across all economic groups in the United States in comparison to their English peers, not just among the poor who are generally seen as having more health problems.
Except for cancer, people with less income and education in both of the nations were more likely to report being sick than those with more income and education. Because of the differences between the two nations, those at the top of the education and income scale in the United States reported rates of diabetes and heart disease that were similar to those at the bottom of the scale in England.
One can't attribute this difference to a lack of access to health care in the United States because those with much more education and income in the US did about as well as those at the bottom did in England.
Researchers were concerned that any differences in health might be blamed on the higher rates of illness seen among Latinos and African-Americans in the United States, so the study included only non-Hispanic Caucasians in both countries.
Researchers say that the differences in health between the two nations is not fully explained by lifestyle factors, including smoking, drinking, excess weight and poor exercise. Smoking behavior is similar in the two nations, while excessive drinking of alcohol is more common in England.
Obesity is more common in the United States and Americans get less exercise, according to the study. But researchers estimate that those factors account for less than half of the differences seen between middle-age people from the United States and England.
The more recent rise in obesity in England means that fat people there, on average, haven't been as fat for as long as similarly fat people in the United States. This would account for the higher rates of heart disease and diabetes in the United States. More accumulation of years of being overweight gives more time for the effects of the obesity to be felt in insulin metabolism and the circulatory system.
Researchers say that past differences in health risk factors may be one explanation for the disparities seen in the middle-aged people covered by the study.
Rising obesity has occurred in the United Kingdom only recently, with the incidence increasing from 7 percent in 1980 to 23 percent in 2003. Meanwhile, the prevalence of obesity in the United States rose from 16 percent to 31 percent during the same period.
“It may be that America's longer history of obesity or differences in childhood experiences create the problems seen among middle-aged Americans,” said study co-author James Banks, an economist at University College London. “This may mean that over time the gap between England and the United States may begin to close.”
This suggests that health of the middle aged will decline in Britain in coming decades with more heart disease and diabetes.
The growing popularity of statin drugs to control cholesterol combined with the development of other drugs to fight obesity and type II insulin-resistant diabetes will eventually reverse this trend.
This report from the Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS) provides selected key findings from 2004 preliminary mortality data for the United States. The findings come from a substantial portion of the records of deaths that occurred in calendar year 2004 and were received and processed by NCHS as of September 12, 2005. Mortality records are based on information reported on death certificates as completed by funeral directors, attending physicians, medical examiners, and coroners.
The age-adjusted death rate reached a record low 801.0 per 100,000 U.S. standard population (Figure 1). This value is 3.8 percent lower than the 2003 rate of 832.7 (Table 1). All the sex, race, and Hispanic origin groups described in this report showed significant decreases in the age-adjusted death rate between 2003 and 2004.
Declines in deaths are rare. An aging population increases the death rate. So what are the causes of this result?
Heart disease continues to be the leading cause of death, accounting for 27 percent of the nation's deaths in 2004. Cancer was second, at about 23 percent, and strokes were third, at 6 percent.
The good news: The age-adjusted death rate for all three killers dropped. The heart disease rate declined more than 6 percent, the cancer rate about 3 percent, and the stroke rate about 6.5 percent.
If this result holds up as the epidemiologists finish their analysis of 2004 deaths then why is this happening? Could statin drugs and other treatments be causing a drop in heart attacks and strokes? Could advances in cancer treatments be behind the decline in cancer deaths?
"The most striking aspect of the data this year was the intensity or volume of the decreases," said Arialdi Miniño, a statistician with the National Center for Health Statistics at the U.S. Centers for Disease Control and Prevention and the lead author of the report. "This is the largest single-year decrease in the raw numbers of deaths that we've seen since the 1940s."
At some point in the 21st century biomedical science and technology will reach a point where whole body rejuvenation becomes possible. At that point the death rate will drop by orders of magnitude in the course of a decade. Some people are trying to make that day come sooner.
Imagine you could be told two or three or four decades in advance what you are going to die from. Imagine a doctor could tell you that you will die from pancreatic failure 20 years from now barring the development of stem cell therapies or bioengineering technologies for growth of replacement organs. Would it change your attitude toward the urgency of medical research?
I've been predicting for some years that advances in biomedical testing will lead to the ability to predict occurrence of many diseases decades in advance and that this will change public attitudes toward biomedical research funding. A recent report shows another example of how testing can increase accuracy of prediction for disease occurrence. A urine test can identify people of very high risk of kidney disease over a 25 year period.
Routine blood and urine tests may help to predict the risk of end-stage renal disease (ESRD) developing between middle age and old age, reports a study in the May Journal of the American Society of Nephrology.
Abnormal results on the urine "dipstick" test, which detects protein in urine, and a blood test to estimate kidney function can identify patients at increased risk of ESRD—permanent loss of kidney function requiring dialysis or transplantation, according to the study by Dr. Areef Ishani of Minneapolis Veterans Affairs Medical Center and colleagues.
Would your willingness to repeatedly write and phone your elected representatives to ask for increased funding to grow replacement kidneys go up by much if someone could tell you that your kidneys are going to fail 20 years from now?
Think about it this way: Most people who are going to die from kidney failure or lung failure, or other organ failure spend the vast bulk of their lives not knowing exactly which organ or disease is going to do them in or when it will happen. So their support for biomedical research remains diffuse and weak. But if everyone knew what was going to kill them then everyone would have a much more clearly defined stake in the advance of biomedical science and biotechnology.
The higher the test result the higher the predicted risk of eventual kidney failure.
Over 25 years, 1.7 percent of the men developed ESRD or died of kidney disease. On the dipstick test, men who had more than a trace amount of protein in their urine in middle age were at triple the risk of ESRD at follow-up. For those with a stronger positive result, ESRD risk was more than 15 times higher than in men with a normal dipstick result.
The estimated glomerular filtration rate (eGFR)—a rough estimate of kidney function, based on a blood test—also predicted long-term ESRD risk. When the eGFR was abnormally low, risk of eGFR was more than doubled.
The risk of ESRD was especially high when both the dipstick test and eGFR were abnormal-—41 times higher than in men with normal results on both tests. Another routine blood test, the hematocrit level, was unrelated to ESRD risk.
Those people who had 41 times the risk of kidney failure probably had much more than a 50% chance of kidney failure.
Additional factors contribute to the risk of kidney failure.
Several other factors predicted ESRD risk, including age, smoking, blood pressure, low levels of high-density lipoprotein ("good") cholesterol, and blood sugar (glucose) level. Many risk factors for kidney disease are the same as those for heart disease.
Throw in future cheap genetic tests and some more blood and urine tests. Then the accuracy of calculations for risks of death from kidney failure will become even more exact. Ditto for predictions of failures of other organs and body parts.
The ability to predict what is going to kill you will not make each individual support research only on a single disease. People will also find out what is going to kill their parents, their best friends, their kids, their spouses, and acquaintances. Also, people are going to find out what would kill them if their first killer doesn't do it. "Well Bill, your heart's going to give out 15 to 20 years from now and then your kidneys a few years later and then your liver is going to be shot". Suddenly you'll have a laundry list of things you want cures for.
Plus, a lot of chronic diseases don't kill you but are mighty inconvenient and some are quite painful. Suppose teenagers can be told they're at high risk of seborrhea or Crohn's Disease or arthritis or several other diseases that won't kill them but will be with them for decades. Many of those medical problems you start accumulating in your teens, 20s, 30s, and 40s will become predictable to varying extents. Therefore in the future where tests can more accurately predict onset of a large range of diseases even teens will find more reasons to support biomedical research.
Advances in medical tests that increases disease prediction accuracy will create larger interest groups in support of development of cures for all the diseases whose occurrence can be more accurately predicted long in advance of clinical onset. Since advances in testing are happening and will continue to happen for decades to come I'm predicting a growth in the size of interest groups in support of the development of stem cell research, gene therapy, growth of replacement organs, and other cures for diseases. This trend will accelerate the development of treatments that can reverse aging entirely.
April 3, 2006 – If you're middle age and sleep five or less hours a night, you may be increasing your risk of developing high blood pressure, according to a study released by Columbia University's Mailman School of Public Health and the College of Physicians and Surgeons, and reported in Hypertension: Journal of the American Heart Association.
"Sleep allows the heart to slow down and blood pressure to drop for a significant part of the day," said James E. Gangwisch, PhD, lead author of the study and post-doctoral fellow in the psychiatric epidemiology training (PET) program at the Mailman School. "However, people who sleep for only short durations raise their average 24-hour blood pressure and heart rate. This may set up the cardiovascular system to operate at an elevated pressure."
Dr. Gangwisch said that 24 percent of people ages 32 to 59 who slept for five or fewer hours a night developed hypertension versus 12 percent of those who got seven or eight hours of sleep. Subjects who slept five or fewer hours per night continued to be significantly more likely to be diagnosed with hypertension after controlling for factors such as obesity, diabetes, physical activity, salt and alcohol consumption, smoking, depression, age, education, gender, and ethnicity.
The researchers conducted a longitudinal analysis of data from the Epidemiologic Follow-up Studies of the first National Health and Nutrition Examination Study (NHANES I). The analysis is based on NHANES I data from 4,810 people ages 32 to 86 who did not have high blood pressure at baseline. The 1982-84 follow-up survey asked participants how many hours they slept at night. During eight to 10 years of follow-up, 647 of the 4,810 participants were diagnosed with hypertension. Compared to people who slept seven or eight hours a night, people who slept five or fewer hours a night also exercised less and were more likely to have a higher body mass index. (BMI is a measurement used to assess body fatness). They were also more likely to have diabetes and depression, and to report daytime sleepiness.
I've come across other studies on the obesity-sleep connection. If you want to keep the weight off find a way to get enough sleep. See, for example, my posts Sleep A Lot To Avoid Burn-Out From Stress And To Stay Skinny and Mutant Mice With Disrupted Sleep Habits Get Fat.
Get 7 or 8 hours sleep each night so that you'll live long enough to still be alive when rejuvenation therapies are developed.
The brain is going to be the the hardest organ in the body to rejuvenate. We will not be able to replace the brain since it contains our individual identity. So we'll need to repair it in place. By contrast, some day we'll be able to grow replacements for other organs in the body such as the liver, kidneys, heart, or pancreas. Since the brain is the hardest rejuvenation therapy target I'm always heartened by any research that suggests promising avenues for development of brain rejuvenation techniques. A team of researchers in Israel have made discoveries that suggest rejuvenation of the immune system might some day partially slow or partially reverse the aging of brains.
REHOVOT, ISRAEL -- January 16, 2006 -- A team of scientists at the Weizmann Institute of Science, led by Prof. Michal Schwartz of the Neurobiology Department, has come up with new findings that may have implications in delaying and slowing down cognitive deterioration in old age. The basis for these developments is Schwartz's team's observations, published today in the February issue of Nature Neuroscience, that immune cells contribute to maintaining the brain’s ability to maintain cognitive ability and cell renewal throughout life.
Until quite recently, it was generally believed that each individual is born with a fixed number of nerve cells in the brain, and that these cells gradually degenerate and die during the person's lifetime and cannot be replaced. This theory was disproved when researchers discovered that certain regions of the adult brain do in fact retain their ability to support and promote cell renewal (neurogenesis) throughout life, especially under conditions of mental stimuli and physical activity. One such brain region is the hippocampus, which subserves certain memory functions. But how the body delivers the message instructing the brain to step up its formation of new cells is yet unknown.
Schwartz's group believes immune system T cells enter the brain to carry out functions beneficial to the brain. Schwartz already found evidence that immune cells carry away toxins. She now presents evidence that immune T cells stimulate brain stem cells to produce new nerve cells (neurogenesis).
The central nervous system (CNS), comprising the brain and spinal cord, has been considered for a long time as "a forbidden city", in which the immune system is denied entry as its activity is perceived as a possible threat to the complex and dynamic nerve cell networks. Furthermore, immune cells that recognize the brain's own components ("autoimmune" cells) are viewed as a real danger as they can induce autoimmune diseases. Thus, although autoimmune cells are often detected in the healthy individual, their presence there was perceived as an outcome of the body's failure to eliminate them. But Schwartz’s group showed that these autoimmune cells have the potential ability if their levels are controlled to fight off debilitating degenerative conditions that can afflict the CNS, such as Alzheimer’s and Parkinson's diseases, glaucoma, amyotrophic lateral sclerosis (ALS), and the nerve degeneration that results from trauma or stroke.
In their earlier research, Schwartz and her team provided evidence to suggest that T cells directed against CNS components do not attack the brain but instead, recruit the help of the brain's own resident immune cells to safely fight off any outflow of toxic substances from damaged nerve tissues.
In the present study, the scientists showed that the same immune cells may also be key players in the body's maintenance of the normal healthy brain. Their findings led them to suspect that the primary role of the immune system's T cells (which recognize brain proteins) is to enable the "neurogenic" brain regions (such as the hippocampus) to form new nerve cells, and maintaining the individual's cognitive capacity. The research team led by Prof. Schwartz, included graduate students Yaniv Ziv, Noga Ron and Oleg Butovsky, and in collaboration with former graduate student Dr. Jonathan Kipnis and with Dr. Hagit Cohen of the Ben-Gurion University of the Negev, Beer Sheva.
Mice lacking T cells generate fewer new neurons in response to a mentally stimulating environment.
It was reported before that rats kept in an environment rich with mental stimulations and opportunities for physical activity exhibit increased formation of new nerve cells in the hippocampus. In the present work, the scientists showed for the first time that formation of these new nerve cells following environmental enrichment is linked to local immune activity. To find out whether T cells play a role in this process they repeated the experiment using mice with severe combined immune deficiency (scid mice), which lack T cells and other important immune cells. Significantly fewer new cells were formed in those mice. On repeating the same experiment, this time with mice possessing all of the important immune cells except for T cells, they again found impairment of brain-cell renewal, confirming that the missing T cells were an essential requirement for neurogenesis. They observed that the specific T cells that are helping the formation of new neurons are the ones recognizing CNS proteins.
To substantiate their observations, the scientists injected T cells into immune-deficient mice with the objective of replenishing their immune systems. The results: cell renewal in the injected mice was partially restored finding that supported their theory.
In another set of experiments, they found that mice possessing the relevant CNS-specific T cells performed better in some memory tasks than mice lacking CNS-specific T cells. Based on these findings, the scientists suggest that the presence of CNS-specific T cells in mice plays a role in maintaining learning and memory abilities in adulthood.
The use of the immune system to carry away toxic substances could potentially include removal of intracellular and extracellular junk. The removal of such junk is one of the major SENS (Strategies for Engineered Negligible Senescence) categories for the development of rejuvenation therapies. The use of the immune system to stimulate the production of new cells is also another SENS category.
Rejuvenation of the immune system would bring other advantages aside from encouraging neurogenesis. People would become less susceptible to death from infections in old age. Infections would not last as long and one would become less susceptible of getting sick in the first place. Also, a sufficiently sophisticated immune system rejuvenation would cure many auto-immune diseases.
This result illustrates a more general point about rejuvenation therapies: Rejuvenation of some subsystems of the body will cause other subsystems to work better. An aged subsystem will work better if other subsystems become young again. We do not have to make every part of the body younger to make the entire body function more youthfully overall.
Using data from the Framingham Heart Study which follows several thousand people in Framingham Massachusetts Dutch researchers found that running 30 minutes a day 5 days a week will add 3.5 to 3.7 years to one's life.
"This shows that physical activity really does make a difference -- not only for how long you live but for how long you live a healthy life," said Oscar H. Franco of the Erasmus M.C. University Medical Center in Rotterdam, who led the study, published yesterday in the Archives of Internal Medicine. "Being more physically active can give you more time."
The researchers calculated the effects of low, moderate or high levels of physical activity on life span, accounting for the possible effects of factors such as age, sex, education, and whether they smoked or had serious health problems.
People who engaged in moderate activity -- the equivalent of walking for 30 minutes a day for five days a week -- lived about 1.3 to 1.5 years longer than those who were less active. Those who took on more intense exercise -- the equivalent of running half an hour a day five days every week -- extended their lives by about 3.5 to 3.7 years, the researchers found.
This result strikes me as an argument for getting a dog that is big enough to run as fast as you can. Those little pint-sized dogs just can't keep up to a human running at full gait. Dogs are great personal trainers, coming to you every day trying to get you to take them for a walk or run.
Predictors for exceptional human longevity may include birth order, place of birth and early-life living conditions, according to a recent Society of Actuaries (SOA) study that suggests there are several factors linked to one’s longevity. The data indicates that first-born daughters are three times more likely to survive to age 100 compared to later-born daughters. The chances for exceptional longevity are minimal for sons having a birth order of four to six compared to those born earlier or later.
The research, developed by the SOA in partnership with researchers at the Center on Aging and the National Opinion Research Center at the University of Chicago, evaluated detailed family data for nearly 1,000 centenarians born in the U.S. between 1875-1899. Drs. Natalia Gavrilova and Leonid Gavrilov collected data from publicly available computerized genealogies of 75 million individuals identified in previous studies and validated ages and birth dates by linking records to the Social Security Administration Death Master File and reviewing U.S. censuses for years 1900, 1910 and 1920.
“The study supports the idea that early childhood conditions might be important for survival to advanced ages,” said Dr. Natalia Gavrilova. “Limited access to parental care, including attention and supervision, may result in less attention being paid to the health and safety of later-born children, resulting in a higher risk of infections and malnutrition during early childhood.”
The data further suggests that children born to parents who are farmers and childhood residence in the Western region of the U.S. may be indicators for subsequent survival to age 100. The study determined that children of farming parents who lived in the Mountain Pacific and West Pacific regions of the U.S. have a greater chance of surviving to age 100 than those from the Midwest and Northeast areas of the country.
“Without the type of food processing that’s currently available, living on a farm 100 years ago meant fresher food with more nutrient value,” said Thomas Edwalds, Fellow of the SOA and chairman of the project oversight committee. “This very well might correlate to prenatal and perinatal nutrition as factors of exceptional longevity.”
People living to age 100 and beyond represent one of the fastest-growing age groups of the American population, increasing at a rate of about 4.1 percent each year.
“Actuaries are skilled at measuring risks, and this research helps us better understand the predictors of longevity and quantify the implications on society and business,” continued Edwalds. “This research also illustrates that studies on human longevity could be modernized and advanced further by using new computerized data resources such as genealogies.”
Can one use this information in any way? Without knowing the mechanism which cause these effects it is hard to say. Some possible causes of this phenomenon could be managed for better results. For example, one could imagine ways that a woman's body could treat an earlier pregnancy differently than a later pregnancy. During a first pregnancy a woman could have a larger store of minerals and vitamins to give to a fetus. So a woman could compensate with vitamin supplements. But alternatively the immune system of a woman's body could could respond to a succession of pregnancies differently and become poorer at avoiding immune responses to a pregnancy. That'd be harder to do something about.
Infection is also hard to manage. A first born child typically grows up in a home with fewer children than a later born child. So the first born does not have the later children as vectors to give the first born infections. But the later born children have the older earlier born children as sources of pathogens. When the 5 or 6 year old goes off to school, gets infected, and then brings home the infectious pathogen to infect the 1 and 2 year olds then the younger later birth children end up getting hit by more infections which each exact their toll. How to compensate for this? One could imagine that home schooling might reduce the infectious disease risk posed by older children to younger children in the same family. If the kids do not go to school to get dosed with pathogens by other kids then the kids won't bring those diseases home to infect their siblings.
Suppose a big factor in causing the above results is frequency of infections. Let me take this as an opportunity to pitch for one of my favorite public health ideas: Vaccines should be developed for more diseases including the many rhinoviruses (which cause some cases of the common cold). Development of technologies that allow much larger numbers of pathogens to be targetted by vaccines could reduce the frequency of infection during early childhood and later in life and reduce the aging caused by infection. It'd also eliminate many miserable days of being sick.
A research team at Umeå University in Sweden have found that the telomere length influence on aging appears to be inherited from fathers, not mothers.
Telomeres are genetic material with repetitive content at the ends of DNA, and their main function is believed to be to protect the rest of the genetic material from degradation. Telomeres are shortened each time a cell divides, which in broad terms means that the longer a cell’s telomeres are, the longer the individual can live, in theory. A person’s telomeres are shortened with age, which the findings of the study indeed show: telomeres were shortened by an average of 21 nitrogen base pairs per year in the subjects studied.
The study, soon to appear in the U.S. scientific journal PNAS, Proceedings of the National Academy of Sciences, was carried out on 132 healthy subjects in 49 different families with no close kinship to each other in northern Sweden. The subjects consisted of fathers and mothers (mean age 66 years) and their daughters and sons (mean age 37 years). Blood samples were taken, and mononuclear immune cells were culled.
Half of these were simply frozen, while the other half were infected with Epstein-Barr virus (EBV) and cultured for 18-55 days, whereupon the surviving cells were frozen. DNA was then extracted from both cell types using standardized techniques, and the length of the telomeres was ascertained.
The findings show that changes in the length of the telomeres in the cultured cells are determined by the original length of the telomeres, and the length of the telomeres in the second generation, both sons and daughters, proved to be inherited from the father.
Telomeres are caps on the ends of chromosomes. They get shorter each time cells divide. As the telomere caps become really short they start to interfere with cell division. This is one of the causes of aging. Telomere cap shortening is probably an evolved mechanism to reduce the risk of death from cancer. Cancers need to undergo a mutation to activate telomerase to grow longer telomere caps so that the cancer cells can divide many more times than normal cells can.
Given that shorter telomere lengths probably reduce cancer risk it is by no means guaranteed that people who inherit longer telomeres from their father will live longer on average.
I would be curious to know what the mechanism might be to cause telomere length to track with paternal inheritance. Do sperm genes for telomerase expression have a methylation pattern or other circumstance that makes them become active as soon as the sperm and egg meet? Does paternal telomerase regulatory genes get turned on while maternal telomerase regulatory genes are suppressed?
Suppose this finding holds up upon further investigation. The female line of descent still has at least one big unique influence upon longevity: mitochondrial DNA. That comes solely from the female line of descent the vast bulk of the time (though perhaps not always).
The abstract and full paper can be found here.
Also see my previous posts "Telomere Length Indicates Mortality Risk" and "Chronic Stress Accelerates Aging As Measured By Telomere Length".
If the threat of cancer, stroke, heart disease, and other old age diseases aren't enough to scare smokers into quitting how about the threat of becoming dumber as the toxins in cigarette smoke damage the brain?
ANN ARBOR, MI – Smokers often say that smoking a cigarette helps them concentrate and feel more alert. But years of tobacco use may have the opposite effect, dimming the speed and accuracy of a person's thinking ability and bringing down their IQ, according to a new study led by University of Michigan researchers.
The association between long-term smoking and diminished mental proficiency in 172 alcoholic and non-alcoholic men was a surprising finding from a study that set out to examine alcoholism's long-term effect on the brain and thinking skills.
While the researchers confirmed previous findings that alcoholism is associated with thinking problems and lower IQ, their analysis also revealed that long-term smoking is too. The effect on memory, problem-solving and IQ was most pronounced among those who had smoked for years. Among the alcoholic men, smoking was associated with diminished thinking ability even after alcohol and drug use were accounted for.
The findings are the first to suggest a direct relationship between smoking and neurocognitive function among men with alcoholism. And, the results suggest that smoking is associated with diminished thinking ability even among men without alcohol problems.
Avoid neurotoxins. Your brain is your most valuable asset.
Those who think they will live long enough to enjoy the benefits of rejuvenation therapies ought to keep in mind that the brain is going to be the organ that is hardest to rejuvenate. The development of technologies for the growth of replacement organs will allow lots of old parts to get replaced with young parts. But you obviously can not replace your brain without replacing your identity with a different identity. Technologies for brain rejuvenation will come more slowly. Even stem cells therapies that replace dead neurons are far less than ideal because those dead neurons will be taking with them memories and personality elements. Take good care of your brain. Avoid toxins and avoid sports that might give you a concussion. You need for it to last a long time.
Estrogen’s role as an inhibitor of toxic free radicals in cerebral blood vessels may be a key reason why premenopausal women have a lower stroke risk than men.
According to UC Irvine School of Medicine researchers, estrogen has a powerful and positive influence on women’s health by increasing the energy production efficiency of mitochondria – the tiny power plants that provide cells the energy they need to function. And in doing so, the hormone inhibits the mitochondrial production of free radical oxygen molecules. Previous studies have shown that excessive amounts of these radical elements in the body, through a process called oxidative stress, can damage blood vessels and lead to stroke or degenerative disease.
In the UCI study, Dr. Vincent Procaccio of the Center for Molecular and Mitochondrial Medicine and Genetics and colleagues discovered estrogen receptors in vascular mitochondrial cells. To see how mitochondria functioned with deficient estrogen levels, they removed the ovaries from test rats, which suppressed any hormone influence, and identified a significant increase in radical oxygen molecule levels and a decline in the capacity for mitochondria to produce energy. In rats treated with doses of estrogen, however, vascular mitochondria produced energy more efficiently with lower amounts of damaging free radicals.
This effect is probably a product of natural selection. But why? Why would estrogen have been selected for to cause this effect? Why wouldn't testosterone cause the same effect? Or why wouldn't mitochondria always work more efficiently and produce less free radicals even without hormones present?
“We want to find out more how estrogen can protect blood vessels in the brain,” said Procaccio, also an assistant professor of pediatrics. “And when we gain a fuller understanding, we hopefully can figure out how best to realize potential benefits of hormone replacement therapies. Also, learning the mechanisms by which estrogen is beneficial to brain circulation may give us new ideas about how to protect against stroke.”
Spurred by recent findings of the Women’s Health Initiative, there is growing debate over the effects of estrogen and the risk of cardiovascular disease and stroke. While women aged 30 to 50 have about five times less risk of stroke than men, this difference disappears when women reach menopause. Research studies show that estrogen protects animals from experimental stroke, but recent clinical trials with certain hormone replacement therapies in older women did not show protection from stroke.
Study results appear on the online version of Molecular Pharmacology. Chris Stirone, Sue P. Duckles and Diana N. Krause of the UCI Department of Pharmacology assisted with the study. The National Institutes of Health provided support.
Another question: If women live with less free radical production until they hit menopause then why do they catch up with men on stroke rates? They should have less total accumulated free radical damage by the time they lose the estrogen that keeps free radical production down. If that is the mechanism by which stroke risk is lower in women then shouldn't their stroke risk remain lower due to less accumulated damage? Even once they start accumulating damage at the same rate as men they still have less damage accumulated and hence their total accumulated damage should continue to lag.
New Haven, Conn. -- Researchers at Yale School of Medicine and seven other national institutions are recruiting patients to participate in the Kronos Early Estrogen Prevention Study (KEEPS) to look at the effects of estrogen on heart disease prevention.
The study will explore whether beginning hormone therapy in women during the menopausal transition (ages 42 to 58) protects against atherosclerosis, the major cause of heart attacks. Results from a prior study of older women called the Women's Health Initiative (WHI) estrogen plus progestin trial suggested there were few benefits of estrogen on atherosclerosis. The National Institutes of Health halted the study in 2002, but KEEPS will explore issues raised by WHI. Women in WHI were postmenopausal, with a mean age of 62.7, yet most women begin hormone treatment much younger, at the onset of menopausal symptoms.
"Once atherosclerosis is present, it is already too late to prevent it," said Yale principal investigator Hugh Taylor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale. "We think estrogen can help to prevent the disease if started early enough."
Prior to the WHI, most data suggested that hormone replacement therapy was associated with a high degree of protection (30 to 50 percent reductions) against coronary heart disease, mortality and osteoporotic fractures, in addition to a small increase in breast cancer risk.
Once effective anti-cancer treatments are developed the trade-offs of hormone replacement therapies will shift much more clearly toward use of hormone replacements. Also, future cheap DNA testing will allow more accurate predictions of the relative risk of cardiovascular diseases and cancers. Those with lower cancer risk and higher heart disease and stroke risk will be the best candidates for hormone replacement.
But my preferred future solution to the increased risk of heart disease and stroke with age would be to use cell therapies and/or gene therapies to repair the circulatory system. Make the circulatory system young again.
Update: As Sheila reminds me in the comments, a previous post of mine reported evidence that estrogen might not continue to benefit blood vessels in old age. See my post "Estrogen Becomes Vasoconstrictor In Old Age". But perhaps an increase in arginine in the diet could restore the vasodilation effect of estrogen as I discuss in that post.
Severely restricting calories over decades may add a few years to a human life span, but will not enable humans to live to 125 and beyond, as many have speculated, evolutionary biologists report.
"Our message is that suffering years of misery to remain super-skinny is not going to have a big payoff in terms of a longer life," said UCLA evolutionary biologist John Phelan. "I once heard someone say caloric restriction may not make you live forever, but it sure would seem like it. Try to maintain a healthy body weight, but don't deprive yourself of all pleasure. Moderation appears to be a more sensible solution."
Biogerontologist Aubrey de Grey has been making this argument for years. He expects humans to get a much smaller percentage gain from calorie restriction as compared to much smaller creatures.
"With mice, if you restrict their caloric intake by 10 percent, they live longer than if they have unlimited access to food," Phelan said. "If you restrict their intake by 20 percent, they live even longer, and restrict them to 50 percent, they live longer still; but restrict their intake by 60 percent and they starve to death."
Calorie restriction is not a panacea according to Phelan. I agree. A real panacea would make your body young again and not just slow down the rate at which you get old.
"Humans, in contrast, will not have rodent-like results from dramatically restricting calories," he said. "Caloric restriction is not a panacea. While caloric restriction is likely to be almost universal in its beneficial effects on longevity, the benefit to humans is going to be small, even if humans restrict their caloric intake substantially and over long periods of time."
Phelan developed the first mathematical model demonstrating the relationship between caloric intake and longevity, using representative data from controlled experiments with rodents, as well as published studies on humans, diet and longevity. He and Michael Rose, professor of ecology and evolutionary biology at the University of California, Irvine, published their findings in a journal article titled, "Why dietary restriction substantially increases longevity in animal models but won't in humans," published in the August issue of the peer-reviewed journal Ageing Research Reviews.
Phelan says CR might deliver as much as a 7% increase in life but 3% is more likely. So you get two more years.
Their mathematical model shows that people who consume the most calories have a shorter life span, and that if people severely restrict their calories over their lifetimes, their life span increases by between 3 percent and 7 percent -- far less than the 20-plus years some have hoped could be achieved by drastic caloric restriction. He considers the 3 percent figure more likely than the 7 percent.
"The trade-off between calories and longevity appears to be close to a linear relationship, but the slope isn't very steep," said Phelan, whose model predicts the relationship between calories consumed and life span.
Phelan thinks it is not worth it to go through life feeling hungry.
Phelan's conclusion is that the few extra years of life are not worth the suffering necessary to achieve them.
The vast majority do not have the will power to do this in the first place. I bet even if the benefit of long term calorie restriction was shown to be 20 or 30 more years few people could bring themselves to follow a CR diet.
But suppose CR would buy you 2 years of additional life starting in, say, 2034. Well, if rejuvenation therapies hit the market in 2035 then that extra two years could save your life.
"Do you want to spend decades severely limiting what you eat to live a few more years? You will be unhappy and then your life will end shortly after mine ends," Phelan jokes.
Scientists have known for six decades that cutting the caloric intake of rodents by 40 percent or 50 percent results in dramatically longer lives for them.
"You can practically double their life span," Phelan said. "The same result has been found in fish, spiders and many other species. If it works for them, some thought, it should work for us; I'm here to tell you it doesn't."
Phelan, co-author of the book, "Mean Genes," conducted his dissertation at Harvard University 10 years ago on caloric restriction and on why it works in extending the lives of rodents.
"When you restrict the caloric intake of rodents, the first thing they do is shut off their reproductive system," said Phelan, citing a finding from his dissertation. A normal rodent reaches maturity at one month of age, and begins reproducing its body weight in offspring every month and a half. If humans shut off reproduction by severely limiting calories, "our reduction in wear and tear on the body is minimal," he said.
Rodents on CR have continuous bad moods.
The rodents placed on severely restricted diets bit people who tried to hold them, and had an unpleasant demeanor, unlike the more docile animals given more "normal" amounts of food, Phelan said.
"I think about food all the time," he said. "I'm not going to be so extreme that I become the mouse that bites anyone who touches me. My advice about food is be sensible, and don't be a fanatic about it because the payoffs are not worth it."
While the relationship between how much you eat and your life span is not so dramatic, there are very real costs of being overweight -- including greater risk for heart disease and other life threatening illnesses, Phelan said.
The human data factored into the mathematical model include the caloric intake of people in Japan, and their longevity, compared with sumo wrestlers, who consume more than twice the normal male diet, and men in Okinawa, Japan, who consume less than the average Japanese male.
We need rejuvenation therapies. The idea of finding a way to slow aging with CR or sirt1 or the latest hope Klotho all seem like misplaced hopes to me. Klotho may eventually deliver the same (limited) benefit as CR but without the perpetual hunger and might be worth taking some day. But we really need gene therapies, cell therapies, immunotherapies that can remove extracellular junk, and other therapies that can do repair.
Long-term hormone therapy used earlier in menopause is associated with fewer wrinkles and less skin rigidity in postmenopausal women, Yale School of Medicine researchers report in the August issue of Fertility and Sterility.
"These benefits were seen in women who had consistently used hormone therapy and had been in menopause for at least five years," said Hugh S. Taylor, M.D., associate professor in the Division of Reproductive Endocrinology and Infertility in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.
"We don't believe hormone therapy will make wrinkles melt away once they're already there, but the results of our study shows that hormone therapy can prevent them. Hormone therapy makes wrinkles less severe and keeps skin more elastic," Taylor added. Taylor and his co-authors compared 11 women who had not used hormone therapy to nine long-term hormone therapy users. Demographics including age, race, sun exposure, sunscreen use, tobacco use and skin type were similar. The researchers made visual assessments of wrinkle severity at 11 facial locations. A plastic surgeon with no knowledge of which women were using hormone therapy rated the number and severity of wrinkles using a Lemperle scale.
The team also measured skin elasticity using a durometer.
They found that rigidity was significantly decreased in hormone therapy users compared to nonusers at both the cheek (1.1 vs. 2.7) and forehead (20 vs. 29). Average wrinkle scores were lower in hormone users than in non-hormone users (1.5 vs. 2.2) on the Lemperle scale.
Taylor said that what is happening in the skin may be reflective of the functioning of other organs such as the heart and bone, which might also be benefiting from estrogen therapy. The results suggest that hormone therapy keeps the skin looking younger and healthier and may have cosmetic benefits if started early. Hormones seem to keep the skin healthy, but can't reverse present skin damage.
Both male and female hormone replacement therapies for anti-aging might increase cancer risks. But if true that is yet another argument for development of effective anti-cancer treatments. Once the various types of cancer become easily curable we will be able to get the benefits of hormone replacement therapies while avoiding many of the risks.
A research team with members from UC Berkeley, the Max Planck Institute in Leipzig Germany, Harvard, and Lawrence Berkeley National Laboratory have examined gene expression patterns of different regions of young and old human and chimpanzee brains using DNA microarrays and found that the frontal cortex where most higher levels of thinking get done ages more rapidly and in ways distinct from other parts of the brain.
No matter how healthy a life one leads, no person has managed to live much longer than a century. Even though the advances of the modern age may have extended the average human life span, it is clear there are genetic limits to longevity. One prominent theory of aging lays the blame on the accumulation of damage done to DNA and proteins by “free radicals,” highly reactive molecules produced by the metabolic activity of mitochondria. This damage is expected to reduce gene expression by damaging the DNA in which genes are encoded, and so the theory predicts that the most metabolically active tissues should show the greatest age-related reduction in gene expression. In this issue, Michael Eisen and colleagues show that the human brain follows this pattern. A similar pattern—which, surprisingly, involves different genes—is found in the brain of the aging chimpanzee.
The authors compared results from three separate studies of age-related gene expression, each done on the same type of DNA microarray and each comparing brain regions in young versus old adult humans. In four different regions of the cortex (the brain region responsible for higher functions such as thinking), they found a similar pattern of age-related change, characterized by changes in expression of hundreds of genes. In contrast, expression in one non-cortical region, the cerebellum (whose principal functions include movement), was largely unchanged with age. In addition to confirming a prediction of the free-radical theory of aging (namely, that the more metabolically active cortex should have a greater reduction in gene activity), this is the first demonstration that age-related gene expression patterns can differ in different cells of a single organism.
Since the paper was published in PLoS Biology you can read the full paper online for free. One section of the paper referring to other studies on brain aging makes mention of some depressing results from another study on brain aging.
Exactly how macromolecules damaged by ROS may lead to aging has been studied in detail in recent years, and the human brain has been intensively examined in this regard because of its overall importance in human senescence. For example, up to one-third of the proteins in the brains of elderly individuals may be oxidatively damaged, and these damaged proteins have been shown to sometimes have diminished catalytic function [3,6]. One recent study of aging in the human brain demonstrated that oxidative damage to DNA can be caused by mitochondrial dysfunction, and tends to accumulate preferentially in some areas of the genome that include promoters, resulting in lower levels of transcription  (possibly due to loss of transcription factor or other protein binding [8–10]). In this same study, genome-wide patterns of aging-associated gene expression change in one region of the human brain cortex (the frontal pole; Figure 1) were measured using DNA microarrays, and genes that had decreased transcription with age were shown to be the ones that are most susceptible to oxidative damage . Since different regions of the human brain have been shown to accumulate DNA damage at different rates [11,12], it is reasonable to suppose that these different regions may show different gene expression changes with age as a result.
Leave aside for the moment the fact that aging eventually kills us. Leave aside that we get more illnesses and disabilities as we age. The fact that our brains decline is extremely distasteful to me. Do you love the thoughts in your mind? Do you love learn and take in new experiences and see new sights and form new memories? Do you love to recall old memories or solve new puzzles? Your ability to do all those things declines with age. That such a large fraction of proteins in the brain are oxidatively damage strongly suggests that the extent of brain aging is quite far reaching. Aging is not just a process that happens to our arms and legs and skin and hair. It happens to our minds, to the very core of our identities. We learn a lot and then our brains gradually decay and even while we are alive part of us dies and the rest us our identity becomes impaired. How repugnant.
The cerebral cortex regions showed the same pattern of gene expression changes with aging while other (and notably older) regions of the brain did not show this pattern.
Strikingly, all four regions of cerebral cortex for which we had expression data (prefrontal cortex, Broca's area, primary visual cortex, and anterior cingulate cortex) showed excellent agreement with the aging pattern in frontal pole (Figure 2A; r > 0.8 and p < 0.02 for each). We note that the true similarity of aging patterns in these regions is likely to be even stronger than is indicated by the correlations because, as mentioned above, approximately 15% of our genes are expected to be false positives with no true aging-related changes. In sharp contrast to cortex, the cerebellum and caudate nucleus showed far less agreement with frontal pole (Figure 2A; |r| < 0.1 and p > 0.4 for each). These results have several implications. First, the agreement between frontal pole and four regions of cortex indicates that we were able to accurately measure the direction of gene expression changes with age for most genes, even with only three samples from each region; thus the age range, number of samples, etc., are all sufficient to reflect the pattern of gene expression changes previously reported in frontal pole . Second, we can have even greater confidence in the results from frontal pole , because they have been independently reproduced (albeit in different brain regions). Third, and most importantly, the human brain appears to have different aging patterns in cerebellum and caudate nucleus than in cortex. The fact that our four cortex samples all show strong correlations with frontal pole is akin to having a positive control, and it allows us to interpret the lack of correlation in cerebellum and caudate nucleus as evidence suggesting a difference in aging patterns, as opposed to several more trivial explanations (e.g., too few samples).
Think about this result from an evolutionary perspective. The frontal lobe has developed most recently. Its development was a big selective advantage. One way to see this result is that our frontal lobes have been "overclocked" because making ourselves think faster allowed us to get more food, defend ourselves, and leave more progeny. I'm speculating here but perhaps our frontal lobes operate faster and wear out more quickly because there was a net selective advantage to turning up the metabolic rate of the frontal lobe because the faster thinking helped us more than the accelerated aging hurt us.
I see the brain as by far the toughest challenge for the development of rejuvenation therapies. For many parts of the body the simplest approach to rejuvenation will be parts replacement. Once tissue engineering and stem cell research advance far enough we'll be able to replace bad parts just as mechanics do with old cars. Got old failing kidneys dodgy lungs ruined by emphysema? Grow new ones. Is your liver shot? If you don't want to get a whole new liver then send in stem cells that programmed to gradually replace the existing cells with new ones. Got liver scar tissue that doesn't want to go away? Send in cells programmed to eat it up to make room for new liver cells made from stem cells. But the brain's three dimensional network of neural connections defines who you are. Put a new brain in place of your own and that body will no longer be you for most practical purposes.
To rejuvenate the brain each cell in the brain must be repaired. But the scope of such a repair job is enormous. While estimates on the number of neurons in a human brain vary the range goes from 10 billion to 100 billion or 100 billion to 200 billion with the number of neuroglial support cells ranging from 5 to 10 times the number of neurons or perhaps 50 to 100 time sthe number of neurons. So we might have a half trillion or even a trillion cells in our brains, all aging and accumulating DNA mutations, intracellular lysosomal junk, and other damage. To develop methods repair all those cells right in the brain is an enormous scientific and engineering challenge.
While stem cell therapy gets a great deal of press (and deservedly so) and while stem cell therapy does have a crucial role to play in brain rejuvenation stem cells can not do most of the brain repair job. Much of brain rejuvenation probably requires highly advanced gene therapy delivery methods and basically DNA programs to send into cells to carry out repair tasks. Future advances in nanotechnology will eventually produce nanobots that can carry out many brain repair tasks. But to repair DNA we need gene therapy to send in corrective sequences to replace mutated sequences and deleted sequences.
If you treasure your ability to think and your mental identity then support a rapid increase in the rate of development of gene therapies and other therapies aimed at brain rejuvenation.
Nicholas Wade of the New York Times reports on how the use of carbon-14 dating of cellular DNA by Jonas Frisen shows that most cells in the body are less than 10 years old. (same article here and here)
But Frisen, a stem cell biologist at the Karolinska Institute in Stockholm, Sweden, has also discovered a fact that explains why people behave their birth age, not the physical age of their cells: A few of the body's cell types endure from birth to death without renewal, and this special minority includes some or all of the cells of the cerebral cortex.
Most molecules in a cell are constantly being replaced but the DNA is not. All the carbon 14 in a cell's DNA is acquired on the cell's birth date, the day its parent cell divided. Hence the extent of carbon 14 enrichment could be used to figure out the cell's age, Frisen surmised. In practice, the method has to be performed on tissues, not individual cells, because not enough carbon 14 gets into any single cell to signal its age. Frisen then worked out a scale for converting carbon 14 enrichment into calendar dates by measuring the carbon 14 incorporated into individual tree rings in Swedish pine trees.
Having validated the method with various tests, he and his colleagues reported the results of their first tests with a few body tissues in the July 15 issue of Cell. They say cells from the muscles of the ribs, taken from people in their late 30s, have an average age of 15.1 years.
The epithelial cells that line the surface of the gut have a rough life and are known by other methods to last only five days. Ignoring these surface cells, the average age of those in the main body of the gut is 15.9 years, Frisen found.
Read the full article for more details on the average age of various types of cells. Note that the vast majority of neurons have existed since childhood. The need to rejuvenate existing neural cells makes brain rejuvenation by far the hardest part of the total rejuvenation therapy development puzzle.
While the researchers found that in some parts of the brain the average cell age was less than the age of the person in the visual cortex the brain was about the same age as the person.
They found that all of the samples taken from the visual cortex, the region of the brain responsible for processing sight, were as old as the subjects themselves, supporting the idea that these cells do not regenerate. "The reason these cells live so long is probably that they need to be wired in a very stable way," Frisén speculates.
Keep in mind that just because a cell divided, say, 7 years ago that doesn't make it youthful. The duration of time since a cell was created from mitotic division is not a measure of the cell's functional age. The damage done to parent cell DNA is inherited by the two cells that are produced when a cell divides. Therefore newly created cells in older organisms will function more like old cells. Also, chromosome telomere caps get shorter each time cells divide and this limits how many times cells can divide. A 7 year old stem cell is of no use if it can no longer divide when damage occurs in joints, muscles, blood vessels, or other components of the body.
The fact that on-going cellular division makes most cells chronologically young and that old cells divide less well actually presents an opportunity for the development of rejuvenation therapies. The development of technologies for producing youthful adult stem cells will provide sources of youthful and healthier stem cells cells to replace the older and less healthy cells that accumulate in our bodies as we age. Since older stem cells divide more slowly rejuvenated stem cells introduced into various parts of the body would out-compete and gradually displace the older cells. Then since most cells are, as reported above, not all that old gradually over a period of several years many more specialized cells (again, blood vessel lining, skin cells, gut cells, etc) would get produced from the healthier introduced stem cells. So gradually a larger fraction of our bodies would become young again.
This latest result supports arguments for an acceleration of the development of stem cell therapies. But we still need to develop gene therapies and other therapies aimed at repairing existing aging neurons and glial support cells in situ, meaning right in the brain. Stem cell therapies and gene therapies are probably the two most important Strategies for Engineered Negligible Senescence (SENS).
Joint pain, especially in the knees, is a common complaint in older patients and can impact quality of life. A team of researchers recently set out to examine how often knee pain is accompanied by pain elsewhere in the body and whether the presence of multiple joint pain affects older patients' general health and psychological status. Their findings, published in the August 2005 issue of Arthritis & Rheumatism, indicate that most people with knee pain also have pain at other sites and these patients tend to have more limited physical function and suffer more from depression and anxiety.
Led by Peter Croft of Keele University in Keele, UK, the authors surveyed a total of 5,364 patients aged 50 years or older who were registered with 3 general practices in North Staffordshire, UK. Each participant completed a questionnaire that included a body manikin on which they shaded any areas where they had experienced pain for one or more days during the last month. Pain was categorized into regions, which included: knee, neck, hand, lower back, hip, and foot and ankle. Based on where the pain occurred, participants were then grouped into (i) those with no pain at all, (ii) those with knee pain, either alone or with pain in 1 or 2 or more locations elsewhere, (iii) those with no knee pain but with pain in 1, 2 or 3 or more locations other than the knee.
A standard health survey used to determine the influence of pain elsewhere on general health was also completed, as well as an index to measure pain and disability specifically related to the knee. Obesity, anxiety and depression, all of which are linked to widespread pain, were also measured using various scales.
Of those surveyed, slightly more than one-third (1,909) ended up in the no pain group, 41% (2,210) in the knee pain group, and 23% (1,245) in the pain elsewhere group. Decreased physical function increased with the number of pains in the body, both in the knee and elsewhere. In those with at least 3 pain regions, the subgroup that included knee pain had worse physical function. This group was also more likely to be depressed than either those with no pain at all or those who had pain in a location other than the knee, even if it was in 3 or more regions.
Knee pain occurs in pain clusters with involvement of other regions of the body.
The results indicate that knee pain does not tend to occur by itself, and that when it occurs with pain in other regions, it is associated with poorer general and psychological health. In addition, the results suggest a link between the extent of pain in the body and the impact of pain in a particular region. "We have shown that knee-specific pain and disability are actually worse in the presence of pains elsewhere than the knee, even after accounting for poorer psychological health," the authors state.
"The practical importance of our findings is that the presence and extent of pain in other sites may be an important determinant of outcome in patients who present with knee pain, just as it appears to be in those who present with back pain [as shown in previous studies]," the authors conclude. In addition, they note that managing pain in one region such as the knee (with local treatments such as physiotherapy or total knee replacement) might have beneficial effects on the general perception of pain and on the frequency and impact of pains elsewhere in the body.
Do the various pains have a common cause? Does chronic pain indicate a generally faster rate of aging?
I'd like to see a follow-up of this study with people over the age of 50 where stem cells get extracted from knees and other regions of pain and also from the blood. The goal would be to measure telomere lengths and compare them between people with and without pain to see if people with more pain are biologically older than age equivalent people who suffer less pain. Telomeres are caps on the ends of chromosomes and their lengths provide an indication of how many times a cell has divded. The more times a cell divides the shorter the telomeres get. I bet that the people with more chronic pains have shorter telomere lengths. Also, I bet that people with shorter telomere lengths will have lower life expectancies on average.
A study that looks for correlations between stem cell age and extent of aches and pains would provide evidence for whether development of stem cell treatments should gain priority in treatment of arthritis and other diseases that cause pain with age. Advocates for Strategies for Engineered Negligible Senescence (SENS) such as Aubrey de Grey argue that it would be more productive to develop rejuvenation therapies than to try to develop treatments for every disease of old age. If aches and pains are the result of cellular aging and of a lack of young stem cells to supply replacements for repair then more rapid development of rejuvenating stem cell therapies would provide better solutions for the pains of old age than surgery, anti-inflammatory drugs, anti-pain medication, and other current approaches.
For why I expect the people with more pains to have shorter telomeres and older stem cells see my previous posts "Telomere Length Indicates Mortality Risk", "Chronic Stress Accelerates Aging As Measured By Telomere Length", and "Aubrey de Grey On Stem Cell Reseeding For Aging".
Tomas A. Prolla of the University of Wisconsin found that mice genetically engineered to undergo more rapid mutation of mitochondrial DNA aged at a much more rapid rate and experienced cell loss, especially in cells that divide rapidly.
Using mice genetically altered to have a deficiency in a protein that proofreads mitochondrial DNA and thus accumulate genetic mutations at a higher rate than unaltered mice, the group led by Prolla found evidence that programmed cell death, known as apoptosis, was greatly accelerated. The altered mice exhibited obvious hallmarks of aging - including graying, hair loss and atrophied muscle and bone - at a pace much faster than the typical laboratory mouse.
"It's like a broken spellchecker," says Prolla. "By introducing a malfunction in the (genetic) proofreading domain, these mutations accumulate much more rapidly."
The new work lends support to one of the two leading theories of how animals, including humans, grow old and die. It supports the theory that apoptosis or programmed cell death underpins aging. A competing theory holds that oxidative stress - the body's reaction to oxygen and the production of reactive, cell-damaging molecules known as free radicals - is responsible for the aging process.
According to the new Science report, markers of oxidative stress did not parallel the accumulation of mitochondrial genetic mutations. Instead, the group found evidence that indicated accelerated cell death, especially in tissues characterized by rapid turnover of cells, occurred as mutations mounted in the mitochondrial DNA.
"We found no evidence of oxidative stress," Prolla explains. In fact, the team noted less oxidative stress in some tissues - the liver, for example - which suggests that accumulated genetic mutations in mitochondria slow metabolism. In turn, that change prompts cells to produce fewer of the reactive free radical molecules.
The symptoms of aging become pronounced with the loss of some critical cells, notably adult stem cells from some tissues and that are essential for replacing cells that die. "If these stem cells are lost, tissue structure and the ability of tissue to regenerate are impaired," Prolla explains. "We have observed that in tissues like bone marrow, intestine and hair follicles."
The altered mice used in the study were created by manipulating mouse embryonic stem cells to produce mice with the defective DNA proofreading protein. The mice develop normally, but age rapidly and develop such things as age related heart dysfunction, hair loss, loss of immune cells, anemia, and loss of male germ cells that lead to reduced sperm production and infertility.
We need constant supplies of replacement cells. Aging of stem cell reservoirs in the body are especially harmful because stem cells divide to produce a very large range of replacment cell types throughout the body.
Prolla thinks an obvious next step would be to genetically engineer mice to have a lower rate of accumulation of mitochondrial DNA mutation.
Prolla suggests that new studies of mice engineered to have fewer than normal mitochondrial DNA defects or improved mitochondrial function may pave the way for strategies to retard aging. "The idea would be to reduce the level of cell death and improve function. If that pans out, then we can begin to think about pharmaceutical interventions to retard aging by preserving mitochondrial function."
Stem cell therapies could replace the stem cells lost due to aging. That would provide enormous benefit. Also, growth of new replacement organs would allow entire aged organs to be replaced by youthful organs. But we also need the ability to send in gene therapy to repair or replace the mitochondrial DNA of aged cells. Look at brain cells. Unless you want to entirely forget the past you don't want to just replace old nerve cells because those old cells hold memories and have been conditioned to perform various tasks.
Mitochondrial DNA is the genetic Achilles Heel of eukaryotic cells (and human cells are eukaryotic because they have specialized compartments such as the nucleus and mitochondria). Eukaryotic cells have mitochondria which are sort of like mini-cells within cells. These mini-cells (usually called organelles) are specialized to carry out the task of breaking down sugar to produce energy molecules (ATP and NADH) used elsewhere in cells to provide energy to carry out just about all cellular tasks. The problem with mitochondria is that they have their own DNA which is exposed to free radicals generated by the breakdown of sugars. Damage to the DNA by those free radicals probably cause the mitochondrial DNA to accumulate mutations at a faster rate than nuclear DNA.
Biogerontologist Aubrey de Grey proposes the development of modifications of the 13 mitochondrial DNA genes to allow those genes to be moved to the cell's nucleus. This would reduce the rate at which the mitochondrial genes get mutated and therefore delay the decline of cellular energy production as cells age. Cells with better protected mitochondrial genes would continue to produce energy for many more years (perhaps decades longer) and therefore general cellular aging would be much slowed. This latest report provides evidence that strongly suggests Aubrey's proposal would help.
Hopefully Prolla's report will be seen by the scientific community as a reason to do the work necessary to genetically engineer mitochondrial genes to move them into the nucleus.
STANFORD, Calif. – Older people are more prone to infections and have a higher risk of developing leukemia, and now researchers at Stanford University School of Medicine have one hint as to why that may be. The group found that in mice, the bone marrow stem cells responsible for churning out new blood cells slow down in their ability to produce immune cells, leaving older mice with fewer defenses against infection.
This result is not the least bit surprising. The decrease in the ability to divide probably happens in every stem cell type in the body as animals and humans age.
These new findings, published in the June 20 online issue of Proceedings of the National Academy of Sciences, add to mounting evidence that many pitfalls of aging result from either older stem cells or stem cells responding to their older environment.
“Aging results in a diminished capacity of the body to maintain tissue and organ function. Since we know the cells mediating this maintenance are stem cells, it doesn’t take a great leap of faith to think that stem cells are at the heart of that failure,” said Derrick Rossi, PhD, postdoctoral scholar and co-first author on the paper with postdoctoral scholar David Bryder, PhD.
In addition to producing fewer immune cells, the older blood-forming stem cells were actively using genes known to be involved in leukemia, a group of cancers that affect blood cells. This could be one reason why older people are more prone to developing certain forms of leukemia.
The role of stem cells in cancer formation is suspected in a number of cancer types. Stem cells divide a lot and cell division is an error-prone process. As compared to cell types that divide less often stem cells are at greater risk of accumulating errors in genetic and epigenetic information. Those errors increase the risk of cancer as we age.
Senior author Irv Weissman, MD, director of the Stanford Institute for Cancer and Stem Cell Biology and Medicine, said one surprise came when the group transplanted older stem cells into younger mice. Those cells continued to behave like old stem cells, producing fewer immune cells and turning on cancer-causing genes. From previous work in mouse muscle cells, he said he expected the blood-forming stem cells to resume a more youthful life once transplanted into younger mice.
This work could eventually lead to new ways of improving immune function in older people or of preventing leukemia. As one example, Weissman said that by understanding the difference between older and younger stem cells it may be possible to prompt old cells to act young again, reviving their ability to produce immune cells.
What we really need is the ability to replace aged stem cells with younger and less defective stem cells. If we could replace old stem cells we'd gain many benefits including better repair capabilities, reduced risk of cancer, and better function in systems such as the immune system that require new cells to be made to respond to constantly changing threats and conditions.
Whether rejuvenation of existing aged stem cells will turn out to be practical depends on what is causing them to act aged in the first place. If a fairly small number of types of mutations or changes in epigenetic information are causing stem cells to age then perhaps gene therapies could eventually be developed to go in and fix the mutations. But if the accumulated problematic damage involves a wider range of locations in the genome then gene therapies aimed at doing repair to individual cells would need to repair too many places and the size of the genetic programming delivered by the gene therapies might end up too large to fit in any gene therapy delivery package.
My guess: For most aged stem cell types delivery of youthful replacement stem cells will likely win out over gene therapies for stem cell rejuvenation.
Copenhagen, Denmark: Women who have a special genetic profile can conceive spontaneously after the age of 45 years, a scientist said at the 21st annual conference of the European Society of Human Reproduction and Embryology today (Tuesday 21 June 2005). Dr. Neri Laufer, from the Haddassah University Hospital, Jerusalem, Israel, told the conference that his team's work to identify a specific gene expression profile linked to later fertility would help understanding of the ageing process, as well as enabling the development of better treatments for infertility in older patients.
Dr. Laufer and colleagues studied a large group of 250 women over 45 who conceived spontaneously. Women are generally not fertile after this age due to ageing of the ovaries, so the scientists thought that there might be some special factor that was allowing these women to conceive. "Mostly they had had a large number of children and also a low miscarriage rate", he said "and these two factors indicated to us that they had a natural ability to escape the ageing process of the ovaries. We decided to see if we could find any differences in gene expression between 8 such women and another 6 women of the same age group who had finished their families at the age of 30."
Using gene chip technology, the scientists found that blood samples from the 8 women had a unique pattern of gene expression that did not exist in the control group. The two main groups of genes expressed in these women were involved in apoptosis (cell death) and in DNA repair mechanisms. "These women appear to differ from the normal population due to a unique genetic predisposition that protects them from the DNA damage and cellular ageing that helps age the ovary", said Dr. Laufer. "What we do not yet know is whether this reproductive success is linked with potential longevity." The women were all Ashkenazi Jews but Dr. Laufer's team does not believe that the gene profile is unique to this group. "We already have preliminary results demonstrating similar results from another group", he said. The team intends to study women from different ethnic, and hence genetic, groups and study their genetic fingerprints against those of the first group.
One wonders whether the apoptosis genes were regulated to make cell death more or less likely in the late conceiving women. Did their ovary cells manage to avoid death and therefore hang around longer to reproduce? Or did their bad ovary cells more reliably die and thereby eliminate their harmful influence on neighboring cells? Some biologists theorize that senescent cells and other old damaged cells release free radicals and other chemicals into their environment that damage neighboring cells. So a greater ability to commit cell suicide might provide a net benefit in the reproductive tract.
These women who have babies later in life who also have repair enzymes unregulated probably have longer average life expectancies. Study of the genetic differences between them and women whose repair enzymes are highly expressed could lead to discovery of genetic variations which upregulate repair enzymes and proteins and RNA fragments which are involved in repair upregulation.
While women who have babies at late ages might have longer life expectancies there is a more obvious group to investigate for life extending genetic variations: really old people. A comparison of gene expression profiles between 90+ year olds and these late reproducing women might yield some insights into which gene expression profiles are most valuable for longevity. Also, really old women could be asked what age they gave birth to their last child.
As DNA sequencing technologies continue to drop in price the rate of search for genetic variations which influence longevity will accelerate. This will lead to identification of proteins that regulate repair and other processes that influence longevity. Any proteins that are involved in DNA repair enzyme regulation would be obvious targets for pharmaceutical development. However, drugs that increase longevity are still a distant prospect for a few reasons.
First off, The development of a drug that upregulates repair would be a tough challenge. Ideally the drug would work in all the cells of the body. A long half life would be desirable in order for it to be able to build up in all cells. Such a drug would probably have to be taken for decades in order to provide a large benefit for longevity. So it would need to be very non-toxic with low incidence of side effects.
Second, proving that a supposedly life extending drug will be efficacious is an extremely difficult task. Clinical trials on 30, 40, or 50 year olds that last a few years can't demonstrate what the effect of a drug will be if taken for decades. If a clinical trial was held for decades it would cost too much, the patent on the drug would expire while the trial was on-going, and, well, we'd all be too old (or dead) by the time the benefit was proven. So, er, who cares?
Third, the US Food and Drug Administration and similar regulatory agencies in other countries are set up to approve drugs that treat or prevent specific diseases. These agencies do not treat aging as a disease. A life extending drug would need to provide some measurable benefit on the incidence of diseases in shorter time frames. While cholesterol lowering drugs and blood pressure lowering drugs extend life they do so by changing metabolisms for purposes that very directly reduce the risk of well characterized diseases. What quickly measurable benefit would up-regulation of DNA repair enzymes bring? Can anyone think of anything? I can't off the top of my head.
While I'd happily take drugs which slow the rate of aging I'm expecting to see treatments that repair and reverse aging before drugs that slow the general rate of aging. The push to develop, for example, stem cell therapies is so great that I expect many useful stem cell therapies to come to market in the next 10 years and probably two or three times more in the following 5 years and again in the following 5 years. But I do not expect any general aging deceleration drug to hit the market in the next 10 years and I'm not certain about the prospects for such drugs in the following 10 years.
The mitochondria are a subcellular organelle (a sort of cell within a cell) that break down sugar to generate energy molecules used throughout the cell. Clay F. Semenkovich, MD at the Washington University School of Medicine and colleagues report that failures in mitochondria due to aging are suspected of causing atherosclerosis and heart disease.
The research team genetically engineered mice to have especially leaky mitochondria in their blood vessel cells. It found that although normal mice very rarely acquire atherosclerosis, the mutant mice all developed the disease, even when fed on a low-fat, low-cholesterol diet. The results of the experiment appear this week in Nature.
They speculate that an increased flow of reactive oxygen damages the blood vessel's walls. The body then mounts an immune response to repair this damage, and scientists have already established that cells trying to fix arterial damage can create problems. These immune cells attract a form of cholesterol that sticks to arterial walls, forming plaques.
Mentally I file this under "Totally Unsurprising". Mitochondria have their own DNA for some of their proteins. Some gerontologists (e.g. Aubrey de Grey) theorize that the mitochondrial DNA (mtDNA) acts as a sort of Achilles Heel in cellular metabolism and cellular aging. Very reactive chemical compounds get generated in mitochondria by breaking down sugar and some of those compounds occasionally break loose and fly into the mtDNA causing damage. So mtDNA might accumulate damage at a much faster rate than DNA in the nucleus.
The increased rate of mutational damage to mitochondrial DNA eventually disables some of the genes that a mitochondrion needs to generate energy. Given that many other mitochondria in a cell could step in to make up the shortage of energy from a single damaged mitochondrion one might not expect damage to one or two mitochondria to make much difference. But note how the article talks about reactive oxygen generated by old mitochondria. The same mutations that cause mitochondria to stop breaking down sugar properly also are suspected of causing mitochondria to generate lots of free radicals. Those free radicals cause inflammation that, through some additional steps, cause hardening and clogging of arteries.
So what to do about this? As one of his Strategies for Engineered Negligible Senescence Aubrey de Grey proposes development of gene therapies to move mtDNA genes into the nucleus where they won't get damaged by mitochondrial metabolism.
This gives us a wonderful opportunity: rather than fixing mitochondrial mutations, we can obviate them. We can make copies of those 13 genes, modified in fairly obvious ways so that the TIM/TOM machinery will work on them, and put these copies into the chromosomes in the nucleus. Then, if and when the mitochondrial DNA gets mutated so that one or more of the 13 proteins are no longer being synthesised inside the mitochondria, it won't matter -- the mitochondria will be getting the same proteins from outside. Since genes in our chromosomes are very, very much better protected from mutations than the mitochondrial DNA is, we can rely on the chromosomal copies carrying on working in very nearly all our cells for much longer than a currently normal lifetime.
This project needs a lot of work, though, even though it sounds simple. The 13 proteins of interest are actually quite difficult for the TIM/TOM machinery to process even when we "tell" it to do so, so we still need to work on making that part easier. But there has been good progress in this area in the past couple of years.
This latest report does not prove that mitochondrial aging is a major cause of plaque build-up in arteries. However, it is certainly consistent with this theory.
The development of gene therapy to fix the problem with mtDNA mutation accumulation still lies many years in the future. Semenkovich is looking for ways to change the amounts of omega 3 and omega 6 fatty acids available in cell walls in hopes that the inflammation response can be reduced so that perhaps the development atherosclerosis will be slowed.
"It would be interesting to figure out how to take essential fatty acids, get them into the vessel wall and see if you could treat atherosclerosis that way," said Semenkovich.
More omega 3 fatty acids from fish might help and I hope Semenkovich succeeds in his investigations. But I'd much rather have gene therapies that would rejuvenate artery and vein wall cells or cell therapies that would replace existing cells with younger and healthier cells.
The June 2005 issue of Biology of Reproduction includes a special paper by a team of Spanish scientists indicating that delayed motherhood in mice results in shorter life expectancy and reduced body weight in their offspring.
Negative effects of late maternal age in women, such as abnormal numbers of chromosomes in their children, are well known. However, other potential negative effects on offspring from delayed motherhood have been only anecdotal.
In what the editors of Biology of Reproduction feel will be a controversial topic of discussion, a team of reproductive biologists headed by Juan Tarín at the Department of Pediatrics, University of Valencia, Spain, presents data in the June issue of the journal that delayed motherhood in mice results in decreased life expectancy and reduced body weight of their offspring.
Several other aspects of reproductive fitness of offspring were assessed, but none showed significant deleterious effects.
This report identifying effects of delayed motherhood on life expectancy and body weight of offspring will surely stimulate inquiries into mechanisms resulting in these disturbing consequences, as well as epidemiological studies in humans, according to the editors of Biology of Reproduction.
The abstract for this report does not provide much detail on the size of the effect.
Do humans born to older mothers suffer decreased life expectancy? If so, by how much? We will have to wait for epidemiological research to answer this question. But epidemiological data is hard to interpret. Women who have babies later in life are, on average, also more able to have babies later in life than women who do not do so. Well, does that ability come as a result of genetic variations that influence life expectancy? We'd need data in women who have multiple children at ages that are far apart from each other in order to compare life expectancy of babies born to the same mother years apart.
Forbes magazine has found that billionaires enjoy only a small advantage in life expectancy over the average American. (same article here)
The average age of death for the 20 billionaires featured in the 2004 and 2005 "In Memoriam" sections of the annual Forbes Billionaires list was 78. We compared this number with the average male life expectancy in the U.S., since all but one of the 20 billionaires on our list that died were males: the billionaires lived 3.5 years longer than average American males. The results would be even more dramatic if we took into account average life expectancies from around the world, since the billionaires on our list are of all different nationalities.
A large part of that difference may not even be due to the ability of the wealth of those billionaires to buy better health care. Writing for Forbes back in June 2004 Dan Seligman pointed out that national health case services have not decreased the gap in life expectancy between upper and lower classes.
But even ten years ago, when this magazine last delved into the topic (FORBES, Jan. 31, 1994), the available answers seemed inadequate. If access was the key, then one would have expected the health gap between upper and lower classes to shrink or disappear with the advent of programs like Britain's National Health Service and America's Medicare and Medicaid, not to mention employer-sponsored health insurance. In fact, the gap widened in both Britain and America as these programs took effect. The 1994 article cited a study of British civil servants--all with equal access to medical care and other social services, and all working in similar physical environments--showing that even within this homogeneous group the higher-status employees were healthier: "Each civil service rank outlived the one immediately below." How could this be?
There are already known substantial differences in life expectancy between the social classes. So even an upper middle class person has a longer life expectancy than average. It is safe to assume that billionaires, like the upper middle class, are a lot smarter than the average person. Seligman points to the research of Linda Gottfredson and Ian Deary which points to average differences in intelligence as an explanation for why the social classes differ in life expectancies.
An explanation not presenting these problems has recently been proposed in several papers by two scholars long associated with IQ studies: Linda Gottfredson, a sociologist based at the University of Delaware, and psychologist Ian Deary of the University of Edinburgh. Their solution to the age-old mystery of health and status is at once utterly original and supremely obvious. The rich live longer, they write, mainly because the rich are smarter. The argument rests on several different propositions, all well documented. The crucial points are that (a) social status correlates strongly and positively with IQ and other measures of intelligence;(b) intelligence correlates strongly with "health literacy," the ability to understand and follow a prescription for disease prevention and treatment; and (c) intelligence is also correlated with forward planning--which means avoidance of health risks (including smoking) as they are identified.
All of Linda Gottfredson's papers on intelligence and health are available on her website. Her paper with Ian Dreary showed that childhood intelligence predicts differences in longevity. (PDF format)
ABSTRACT—Large epidemiological studies of almost an entire population in Scotland have found that intelligence (as measured by an IQ-type test) in childhood predicts substantial differences in adult morbidity and mortality, including deaths from cancers and cardiovascular diseases. These relations remain significant after controlling for socioeconomic variables. One possible, partial explanation of these results is that intelligence enhances individuals’ care of their own health because it represents learning, reasoning, and problem-solving skills useful in preventing chronic disease and accidental injury and in adhering to complex treatment regimens.
That paper also examines the plausible argument the same factors may be causing differences in intelligence and longevity. For example, poor prenatal nutrition would both prevent the brain from developing optimally and also prevent other organs from developing properly. Improperly developed organs would tend to fail sooner and therefore contribute to lower life expectancy. But some of the biochemical environmental factors that hobble fetal development are at least partially a consequence of lower intelligence on the part of pregnant women and their mates. A woman of lower intelligence is less likely to make wise food choices, refrain from smoking and drinking while pregnant, and avoid use of dangerous recreational and addictive drugs.
In her paper Life, Death, and Intelligence Gottfredson points out that many activities that influence life expectancy are very cognitively demanding.
Preventing and managing both chronic disease and accidental injury, the leading causes of death today, is a highly cognitive process. Studies of health literacy, which is learning and reasoning applied to health matters, show that less literate individuals have difficulty understanding and adhering to treatment regimens. Lower adherence predicts higher mortality. Accident prevention models reveal that it requires the same information processing skills that job analyses document as distinctive requirements of high-level, complex jobs: for instance, learning and recalling relevant information, identifying problem situations quickly, and reacting swiftly to unexpected situations. Health providers can reduce excess complexity in their communications and treatment regimens. They can also increase cognitive assistance when tasks are inherently complex, such as in the daily self-management of diabetes, hypertension, and asthma.
In her paper Intelligence: Is It the Epidemiologists’ Elusive “Fundamental Cause” of Social Class Inequalities in Health? Gottfredson argues that much of the difference in health outcomes that correlate with socioeconomic status (SES) may be due to differences of intelligence.
Virtually all indicators of physical health and mental competence favor persons of higher socioeconomic status (SES). Conventional theories in the social sciences assume that the material disadvantages of lower SES are primarily responsible for these inequalities, either directly or by inducing psychosocial harm. These theories cannot explain, however, why the relation between SES and health outcomes (knowledge, behavior, morbidity, and mortality) is not only remarkably general across time, place, disease, and kind of health system but also so finely graded up the entire SES continuum. Epidemiologists have therefore posited, but not yet identified, a more general “fundamental cause” of health inequalities. This article concatenates various bodies of evidence to demonstrate that differences in general intelligence (g) may be that fundamental cause.
There are two implications of these results. One implication is bad news for the lower classes. The other implication is bad news for rich folks.
First off, less bright people in industrialized societies have lower expectancies because they make lousier choices and more incorrect decisions about their health and medical care. This is a hard problem to remedy because many of those decisions are made (or not made) every day. A person doesn't take a beneficial prescription drug that is sitting in their medicine cabinet. Or a person ignores an obvious symptom of disease and fails to see a doctor until it is too late. Or a person smokes cigarettes, eats lots of junk food, or abuses drugs or alcohol. Or a person behaves in ways that increase the chance of accidents. There is an endless variety of ways to shorten your life expectancy. Draconian government involvement in the lives of less intelligent people would be required to prevent many of the life-shortening errors which less intelligent people make.
Even if the government could in theory craft less invasive ways to improve the health of the less intelligent it is hard for public policies to be implemented for this purpose. Why? Because the believers in modern liberalism (whether of the leftist or, in many cases, the neoconservative variety) are loathe to admit that we are not all born into this life with equal potential to learn and achieve. I have no solution to offer on that score except to encourage the funding of development of cheaper DNA sequencing methods. In the decades to come DNA sequencing costs will fall to the point where the genotypes for intelligence will be easily identified and the genetic causes of differences in intelligence will become much harder to deny. Then many of the deniers of the truth will start to come around and admit the obvious. At that point the importance and implications of innate differences in cognitive abilities will return to mainstream discourse after an absence of about a hundred years. My guess is this will happen by 2015 or 2020 at the latest.
The second implication is bad news for billionaires. They can't buy much better medical care. They are super rich. They can buy any medical treatments available. But the same incurable diseases that kill most people in industrialized countries kill billionaires as well. The billionaires not only can't take it with them but they also can't use it to substantially delay their departure into the afterlife. There are limits to their buying power because of the deficiencies in our scientific knowledge about human biology.
The lesson here for the billionaires is that if they want to extend their lives the best use of their own wealth is to fund more research and development aimed at developing better treatments. There are research topics which are poorly funded where the development of Strategies for Engineered Negligible Senescence (SENS) could be greatly accelerated by a few tens of millions of dollars. For example, a billionaire could easily fund an effort to shift the mitochondrial DNA genes into the nucleus of some lab mice or rats to then see how much their life expectancies are increased as a result. Another possibility for wealthy philanthropists is to make a big donation to the the Methuselah Mouse Prize to provide greater incentives for scientists to development rejuvenation treatments.
In a similar vein, members of the middle class can individually make better decisions about diet, exercise, and preventive health care. But collectively the middle class can do far more to improve their health in the long run by supporting policy changes by their governments aimed at accelerating the rate of advance of biomedical science and biotechnology. Only advances which produce new methods of curing diseases and reversing aging can produce a large improvement in health and life expectancies.
A group of researchers including well known names Jay Olshansky and Leonard Hayflick are arguing that average American life expectancy may drop due to rising rates of obesity.
Over the next few decades, life expectancy for the average American could decline by as much as 5 years unless aggressive efforts are made to slow rising rates of obesity, according to a team of scientists supported in part by the National Institute on Aging (NIA), a component of the National Institutes of Health (NIH) of the Department of Health and Human Services (DHHS).
The U.S. could be facing its first sustained drop in life expectancy in the modern era, the researchers say, but this decline is not inevitable if Americans — particularly younger ones — trim their waistlines or if other improvements outweigh the impact of obesity. The new report in the March 17, 2005 issue of The New England Journal of Medicine appears little more than a year after the DHHS unveiled a new national education campaign and research strategy to combat obesity and excessive weight.
The new analysis, by S. Jay Olshansky, PhD, of the University of Illinois at Chicago, Leonard Hayflick, Ph.D., of the University of California, San Francisco, Robert N. Butler, M.D., of the International Longevity Center in New York, and others* suggests that the methods used to establish life expectancy projections, which have long been based on historic trends, need to be reassessed. This reevaluation is particularly important, they say, as obesity rates surge in today’s children and young adults.
“Forecasting life expectancy by extrapolating from the past is like forecasting the weather on the basis of its history,” Olshansky and his colleagues write. “Looking out the window, we see a threatening storm — obesity —that will, if unchecked, have a negative effect on life expectancy.”
Note this is not a new idea. Other researchers have made this suggestion. In fact, this expectation is extremely obvious. We know in increasing detail the ways that obesity changes metabolism for the worse.
My reaction: This is a sort of "if all is is equal" sort of study. It is a really big and improbable "If" in my view: If we do not develop drugs and gene therapies and other treatments to reverse the epidemic of obesity and if we develop no ways to reverse the metabolic damage caused by obesity and if we do not develop new rejuvenation therapies then, yes, life expectancies will decline. But of course we are going to develop all of those things. 50 years from now obesity will be a rarety. Rejuvenation therapies will be cheaply and widely available. Life expectancies will be rising rapidly.
In fact, one National Institute of Aging scientist states the obvious in the press release for this study:
Unlike historic life expectancy forecasts, which rely on past mortality trends, the Olshansky group bases their projection on an analysis of body mass indexes and other factors that could potentially affect the health and well-being of the current generation of children and young adults, some of whom began having weight problems very early in life. The authors say that unless steps are taken to curb excessive weight gain, younger Americans will likely face a greater risk of mortality throughout life than previous generations.
“This work paints a disturbing portrait of the potential effect that life styles of baby boomers and the next generation could have on life expectancy,” says Richard M. Suzman, Ph.D., Associate Director of the NIA for Behavioral and Social Research. Indeed, Suzman notes, obesity may already have had an effect. The sharp increase of obesity among people now in their 60s, he suggests, may be one explanation why the gains in U.S. life expectancy at older ages have been less than those of other developed countries in recent years.
“But it is critical to note that the reduced life expectancy forecast by the study is not inevitable, and there is room for optimism,” Suzman says. “Government and private sector efforts are mobilizing against obesity, and increased education, improved medical treatments, and reduced smoking can tip the balance in favor of reduced mortality and continued improvements in life expectancy.”
I do not expect education to help much. What we need is gene therapy to reprogram human metabolism to maintain a skinny body weight. Staying at an ideal weight should be and eventually will be made effortless. The big unknown here is just how fast will effective appetite suppressant drugs be developed? We should treat obesity research as an urgent matter deserving greater research efforts just as cancer and heart disease research are treated. Lowering the incidence of obesity would lower the incidence of heart disease, cancer, and a great many other diseases.
My guess is that obesity is still going to be lowering life expectancies for the next 10 years but certainly not 30 years from now. Just how soon the obesity problem will be solved remains to be seen. My guess is it will be solved in 20 years or less. We could solve it faster with more research money though.
Here is the abstract for the article.
As for why I'm an optimist about future human life expectancies start here to learn about rejuvenation therapies and Strategies for Engineered Negligible Senescence (SENS). Then read here for more on rejuvenation.
Dr. Richard White and colleagues at the Medical College of Georgia have found that in older blood vessels estrogen ceases to be a vasodilator that opens blood vessels and instead becomes a vasoconstrictor that restricts blood flow.
They were studying estrogen's effects on blood vessels, focusing on its impact on the smooth muscle cells that allow blood vessels to contract, thereby regulating blood pressure and blood flow. These researchers found that estrogen targets nitric oxide synthase 1, one of three versions of the enzyme that makes the powerful vasodilator, nitric oxide.
"What we were finding is that estrogen seems to be what you might call a natural nitroglycerin; nitroglycerin also works by making nitric oxide," Dr. White says.
Then they tried to block estrogen's activity by blocking nitric oxide. "What surprised the heck out of me was after we blocked nitric oxide production and added estrogen, we got a contraction," says Dr. White. "Estrogen now had turned into a constrictor agent, an agent that would increase blood pressure."
They looked further and found that normal aging decreases levels of the cofactors L-arginine and tetrahydrobiopterin - both critical to nitric oxide synthase's production of nitric oxide.
Instead of making nitric oxide, estrogen was producing the powerful age-promoting - and apparently vasoconstricting - oxygen-free radical, superoxide.
"At first, I thought it was an artifact," says Dr. White, who recently received a $1.2 million, four-year grant from the NHLBI to pursue his findings. But using a porcine heart that is very similar to the human heart, he and Dr. Barman, along with Dr. David J. Fulton, a pharmacologist in the MCG Vascular Biology Center, found that every time they blocked nitric oxide production, estrogen became a vasoconstrictor.
"Under normal conditions, such as a pre-menopausal woman, this enzyme, nitric oxide synthase, makes nitric oxide," says Dr. White.
"But if you block the production of nitric oxide, this nitric oxide synthase now has a secondary product that normally isn't made in an appreciable form. Now it makes a compound called superoxide. It's an oxidant, and oxidation is bad in general. It causes a lot of cellular damage. But what we also have found is that now, instead of causing relaxation, it causes constriction. So you completely flip-flop the response here."
"One of the things this means is that menopause is a good thing, a sort of revolutionary endocrinology idea," says Dr. White.
"Menopause is adaptive because a woman is not supposed to have as much estrogen when she gets older because it can kill her." He holds up a graph plotting the dramatically dropping rates of tetrahydrobiopterin over a woman's life, a drop that parallels the drop in estrogen levels.
"We have to confirm it," he says of the new grant in which researchers will use different drugs to mimic aging, drugs that knock out L-arginine and tetrahydrobiopterin, to try to create an aged artery and restudy estrogen's impact.
"Estrogen is so powerful; it affects every system in your body. We are looking with tunnel vision at its effect on blood pressure control. What would this do to bone? What would this do to Alzheimer's? What happens to the brain is probably very similar," he says as critical cofactors drop that enable estrogen to relax blood vessels. "This could be a mechanism that would affect practically every system in the body."
The dangers posed by estrogen replacement therapy in older women illustrate a point I've made here before: the reason many compounds decline or increase as we age may well be an adaptation to other changes that are caused by damage accumulation that is aging. Restoring those compounds to youthful levels may raise risks of a variety of diseases. For another case which I suspect is also an example of this same phenomenon see my warning that replacement of older blood with younger blood may reinvigorate many stem cell reservoirs but at the cost of increasing the risk of cancer. Some types of rejuvenating interventions may not be prudent before other types of rejuvenation can be accomplished first. Otherwise, as is illustrated with this report above, the net result can be harmful.
One practical question arises from this study: Can we at least partially prevent the decline in nitric oxide production capability in old bodies by eating more foods that contain L-arginine? Studies of the effects of supplementary L-arginine on the vasodilation of old blood vessels seem like a wise idea. It might be possible to cancel out some of the negative effects of hormone replacement therapy in older women by L-arginine supplementation or some compound that would enhance vasodilation.
If you want to boost your L-arginine intake on speculation that this will increase nitric oxide production then nuts are good sources of L-arginine and hazel nuts, brazil nuts, and walnuts are the richest sources (at least of those nuts listed). See the table 4 at that link for more nuts and their L-arginine content. The reported heart healthy benefits of nut consumption may be coming at least in part from the vasodilatory effects of the L-arginine in them.
Women have longer life expectancies than men in industrialized countries. Slower aging of hearts is one reason for greater female longevity. (same article here)
Research by exercise scientists at Liverpool John Moores University (LJMU) may have an answer to the age old question of why women live longer than men.
On average, women live longer than men and women over 60 are now the fastest growing cohort in today’s ageing society. LJMU’s findings show that women’s longevity may be linked to the fact that their hearts age differently to men’s and do not lose their pumping power as they get older.
David Goldspink, LJMU’s Professor of Cell and Molecular Sports Science explains: “We have found that the power of the male heart falls by 20-25% between 18 and 70 years of age. In stark contrast, over the same period there was no age-related decline in the power of the female heart, meaning that the heart of a healthy 70 year-old women could perform almost as well as a 20 year-old’s. This dramatic gender difference might just explain why women live longer than men.”
The results are based on the findings of the largest study ever undertaken on the effects of ageing on our cardiovascular system. Since the study began two years ago, Professor Goldspink and a team of scientists at LJMU’s Research Unit for Human Development and Ageing have examined more than 250 healthy men and women between the ages of 18 and 80 years.
As we age the whole circulatory system deteriorates. Blood vessels become less elastic and less able to carry blood to muscles and skin.
- Blood pressure increases both at rest and during exercise, because the large arteries become stiffer and less elastic as we age.
- Blood flow to the muscles and skin of limbs also progressively decrease. These changes in the structure of blood vessels occur earlier in men, but women soon catch up after the menopause.
Aging pretty much amounts to going to hell in a handbasket. The spin from some quarters that it brings wisdom, maturity, and contentment is no consolation to FuturePundit. Those spinners mostly just make me feel irritated. Aging brings decline, decay, disorders, diseases, and for many people chronic pain and suffering. As Roger Waters famously put it "but you're older, Shorter of breath, and one day closer to death". We should not meekly accept this fate. We can develop the ability to repair and replace worn out parts. Aging reversal is going to come some day. The question is whether it will come soon enough for each of us and how many chronic maladies will we each have to live with for years before rejuvenation therapies are developed.
In a related study, Prof Goldspink found that the hearts of veteran male athletes (aged 50-70) were as powerful, if not more powerful, than those of inactive 20-year-old male undergraduates.
"The 20-25 per cent loss of power in the ageing male heart can be prevented or slowed down by engaging in regular aerobic exercise."
Okay, let us all go back in our time machines and join the pro tennis circuit when we were only 15 years old. Misplaced your time machine? Darn, I can't find mine either. Therefore we are left with only rather more pedestrian options such as get lots of exercise and eat better food. But it will be a lot easier when stem cell therapy can replace all the lost and tired heart cells and artery cells.
Other studies have suggested that higher vitamin D levels help protect against colon, prostate, and breast cancer, but a long-term study of 50,000 men by researchers at Harvard School of Public Health suggests vitamin D may reduce the risk of all cancers. The study, which is still under review for publication, found that men who consumed higher levels of vitamin D reduced their overall cancer risk by at least 30 percent, according to lead author, Ed Giovannucci. The findings were statistically significant, he said, and a separate study of women is expected to produce similar results.
This is big stuff. Imagine an anti-cancer drug that reduced overall cancer deaths by 30%. It would be hailed as a medical wonder. But it is much better to avoid getting cancer in the first place.
Another interesting angle here is this huge benefit against cancer is coming from a vitamin that is not classified as an antioxidant. For decades researchers have been trying to use antioxidant free radical quenching vitamins such as beta carotene, vitamin E, and vitamin C to reduce cancer, heart disease, and other diseases. The results have been pretty disappointing. Now the biggest potential benefit turns out to be from a vitamin which is most likely operating by a mechanism unrelated to prevention of free radical damage.
Keep in mind that this result will not carry over to the world as a whole. Some populations are consistently exposed to enough sunlight for their skins to synthesize the amount of vitamin D that they need. But a 30% reduction in cancer in America looks to be possible. That would be an enormous boon, both lengthening lives and reducing medical costs.
This latest study does not come as a surprise. It builds upon a larger body of epidemiological evidence for a wide array of benefits from consumption of greater quantities of vitamin D. A previous analysis found that addition of Vitamin D and calcium to grains would reduce the incidences of fractures and colon cancer and save $3 billion per year for a cost of less than $20 million per year.
Currently, the federal government requires that manufacturers enrich cereal-grain products with five nutrients—iron and the vitamins thiamine (B1), riboflavin (B2), niacin (B3), and folate (B9). The total cost to U.S. consumers of adding calcium and vitamin D to the list should be no more than about $19 million a year, Harold L. Newmark of Rutgers University and his colleagues report in the August American Journal of Clinical Nutrition. Conservatively, they calculate, this investment would spare U.S. consumers some $3 billion in direct medical costs from illnesses and injuries stemming from their inadequate intake of calcium and vitamin D.
The human body can generate 10,000 to 12,000 international units (IU) of vitamin D from a half-hour of summer-sun exposure. The National Academies recommend that adults, depending on their age, get from 200 to 600 IU of the vitamin each day.
In practice, however, most people in the United States get a daily intake from food and sun exposure well below that recommended intake, especially during winter. People living in the United States and Europe or farther from the equator have trouble getting enough sun to maintain adequate blood concentrations of the vitamin. When people heed dermatologists' warnings about preventing skin cancer by limiting sun exposure and using sunscreen, they also reduce their vitamin D production.
Even the officially recommended amounts of vitamin D are probably well below the level that would provide maximal benefit. Click through on the following link to read an argument for getting 800 to 1000 IU of vitamin D daily.
Lots of aspects of modern society reduced sun exposure. For example work in office buildings contributes to a reduction in sun exposure and reduced vitamin D synthesis. So does the message from dermatologists to avoid sun as a way to lower the risk of skin cancer. This has led to a debate in medical circles about whether sun exposure increases or decreases net cancer risk. This debate has so upset the dermatologists that vitamin D researcher Michael Holick was forced out of Boston University's dermatology department since he veered too far from accepted orthodoxy among dermatologists about sun exposure. My own view is that moderate sun exposure most obviously decreases net cancer risk and that the evidence is building up to the point that science is going to vindicate Holick. By the way, Holick thinks the top daily safe dose for vitamin D is at least 5000 IU, which is much higher than the current officially recommended maximum daily dose (which is 2000 IU if memory serves).
Another element of modern society that is causing vitamin D deficiency is the migration of darker skin peoples to places further away from the equator. This has put them in environments where their darker skin pigment blocks the sun too much to allow sufficient vitamin D synthesis.
Global location and skin color also affect the amount of vitamin D a person's skin manufactures. UV intensity falls as one moves from the equator toward Earth's poles, increasing latitude. Evolution compensated by selecting for increasingly unpigmented skin in northern populations, says Boston University endocrinologist Michael F. Holick.
Melanin pigment protects the skin from the damage of UV rays but also lowers the skin's production of vitamin D. In the March American Journal of Clinical Nutrition, Holick quantifies this effect: Fair-skinned people who sunburn easily and rarely tan need just 2 to 10 percent as much sun exposure to produce a unit of vitamin D as do people with the darkest skin.
Given that blacks especially have higher rates of lactose intolerance the fortification of milk with vitamin D is not reaching a group most in need of dietary vitamin D.
Consumption of fruits appears to boost the level of the biologically active form of vitamin D in the blood. Though if you do not have enough vitamin D in your body the fruit can not make up for that deficiency.
Vitamin D does protect men from prostate cancer. In the USA and many countries, milk is fortified with vitamin D. Even so, calcium in mik and other foods lowers the amount of usable vitamin D in the body. Eating several servings of fruit a day keeps the level of vitamin D raised.
A high circulating level of the biologically active form of vitamin D (1,25(OH)2 vitamin D [1,25(OH)2D) is known to inhibit formation of cancer in the prostate. Eating a diet high in meat and milk and low in fruit reduces the level of this anti-prostate cancer vitamin. "High intakes of calcium and phosphorus, largely from dairy products, lower circulating 1,25(OH)2D level, and sulfur-containing amino acids from animal protein lower blood pH, which also suppresses 1,25(OH)2D production."
Fortification of foods with calcium alone may well have the effect of lowering the rate of colon cancer while boosting the rate of prostate cancer. One concern I have with the combined calcium and vitamin D food fortification is that the level of vitamin D added needs to be set to be enough to more than cancel any effects of calcium on increasing prostate cancer risk.
It is clear that in America the fortification of only milk with vitamin D is inadequate. The decreased consumption of milk prevents milk from being an avenue for boosting vitamin D in a growing portion of the population. Fortification of other milk products such as cheese and yogurt and even a boost in the level of fortification of milk seems called for. Also, the potential benefit of grain fortification with vitamin D is so large that it warrants urgent consideration. Higher vitamin D in diets would reduce the risk of cancers, type I diabetes, osteoporosis, unexplainable muscle and bone pain, hypertension, a wide array of auto-immune diseases (including multiple sclerosis), and possibly other disorders and diseases as well.
The studies about vitamin D and health are great news. The incidence of several major diseases can be reduced for a trivially low cost. We need many more such discoveries that show how to cheaply improve human health.
T cells are the weakest link in the immune systems of older people, based on a report by Eaton and colleagues in the December 20 issue of The Journal of Experimental Medicine. The authors show that old CD4 "helper" T cells cannot provide the stimulatory signals to B cells that prompt them to make antibodies. Old and young B cells, however, are equally effective if helped by young CD4 T cells. The authors think this may help explain why immunizations are less effective in the elderly.
B cell activation and antibody production are known to be impaired with age in both mice and humans, but it was not clear whether this defect is intrinsic to B cells or is a by-product of declining CD4 T cell helper functions.
Eaton and colleagues transferred young or old CD4 T cells into mice lacking their own CD4 T cells to determine which cells are responsible for the age-related decline in B cell function. They show that B cell activation and antibody production can be restored in old mice if they are infused with young CD4 T cells prior to immunization. On the flip side, young mice infused with old CD4 T cells developed antibody defects, even though their B cells were young. In other words, old B cells function like young ones if provided with signals from young helper T cells. While the mechanism is not completely clear, the authors show that old T cells can travel to the right location in the spleen of the mice, but have fewer of the surface proteins that send stimulatory signals to B cells.
We need the ability to rejuvenate T cells. We also need the ability to rejuvenate the thymus gland that plays a crucial role in immune response.
See my previous post Harmful Reduction In Immune System Cell Diversity With Age. Also, chronic stress more rapidly ages at least part of the immune system. See my post Chronic Stress Accelerates Aging As Measured By Telomere Length.
STANFORD, Calif. – For the first time, researchers at Stanford University School of Medicine have examined how kidneys change at a molecular level with the passage of time. What they found suggests that all human cells age in a similar way, supporting one theory about how cells grow old.
“Until now we really didn’t know what happens when people get old,” said Stuart Kim, PhD, professor of developmental biology and genetics, who led the study that is to be published in the November 30 issue of Public Library of Science Biology. “Our work suggests that there’s a common way for all tissues to get old.”
These findings are contrary to one model for how cells age. This theory holds that because organs have different groups of molecules, they follow different pathways as they age. If this were the case then the aging kidney would look quite different on the molecular level from an aging liver.
Instead the study findings support another model, which suggests that all cells in an animal peter out in the same way. If this were true then researchers would find the same molecular differences between old and young cells from all organs.
In the study, Kim and his group compared which genes are active in kidney cells from 74 people ranging in age from 27 to 92 years. They found 742 genes that become more active as the kidney ages and 243 genes that become less active.
They then did the same experiment using different types of kidney tissue, with one sample from the outer kidney, called the cortex, and the other from the inner kidney, called the medulla. Although these two tissues are both from the kidney, they are as different in function as cells from entirely different organs. The researchers found exactly the same genes varied in old and young samples from these two tissues.
The next obvious experiment would be to repeat this study with tissues from other organs and see if the same genes have changing levels of activity as tissue ages. Do some organs age at more rapid rates? Does this happen for everyone? One might expect some variability between humans due to genetic variants that accelerate aging in particular organs and also due to dietary habits and other habits that impose larger harm on certain organs (e.g. smoking on lungs or drinking on livers or fried meats on intestines).
Note that gene microarrays have gotten so powerful that these researchers were able to check the expression levels of all the known genes in a human cell. Chronological age is not always the same as age as measured by molecular genetic expression profile.
Kim and colleagues then isolated RNA transcripts from the samples to determine the activity of every gene, broken down by age and kidney section, through microarray analysis. Looking for differences in gene expression across the genome, they identified genes that showed a statistically significant change in expression as a function of age. Of 33,000 known human genes on the microarray, 985 showed age-related changes, most showing increased activity. These changes are truly age-regulated, the authors conclude, since none of the medical factors impacted the observed changes in gene expression.
Although cortex and medulla have different cell types and perform different functions, their genetic aging profile was very similar, suggesting a common aging mechanism operates in both structures. In fact, these mechanisms may function broadly, as most of the age-regulated kidney genes were also active in a wide range of human tissues. Other organisms appear to lack these changes, however, prompting the authors to argue that understanding aging in humans will require human subjects.
Most importantly, the genetic profile of the tissue samples correlated with the physiological and morphological decline of an aging kidney. An 81-year-old patient with an unusually healthy kidney had a molecular profile typical of someone much younger, while a 78-year-old with a damaged kidney had the profile of a much older person. Using the power of functional genomics, this study has identified a set of genes that can serve as molecular markers for various stages of a deteriorating kidney and predict the relative health of a patient compared to their age group. These gene sets can also serve as probes to shed light on the molecular pathways at work in the aging kidney, and possibly on the process of aging itself.
I'd love to see a longitudinal study where tissues are taken from a number of elderly people and assayed for gene expression to see if onset of diseases and mortality can be predicted from how far along the cells in a person seem to have aged according to gene expression levels.
One public policy implication of a developed ability to more accurately predict life expectancy is that government-funded old age retirement funds could (not saying they would) offer different ages of eligibility for retirement based on how old a person is measured to be at the molecular level. A highly aged 60 year old could be offered early retirement based on a short life expectancy and a diminished ability to work. At the same time a highly health and functional 70 year old could be told they have to keep working or live off their own savings because all molecular indications are that they have years of healthy vibrant life still left in their bodies. Given that governments face massive unfunded liabilities for old age entitlements programs the ability to distinguish between aged elderly and relatively more youthful elderly could provide governments with a way to lighten their fiscal burdens.
You can read the full research paper free of charge.
Why does the immune system become less effective as we age? One reason is that the thymus gland ages. We need to be able to rejuvenate our thymus glands. But another reason is that the T cells in the immune system get old and mess up in a variety of ways. Certain CD8 T cells divide too much and crowd out other needed T cells.
PORTLAND, Ore. – Scientists at the Vaccine and Gene Therapy Institute at Oregon Health & Science University have made a discovery that helps explain why our immune system worsens with age. The work was led by Janko Nikolich-Zugich, M.D., Ph.D., a senior scientist at the VGTI. The scientists hope this new information can be used to better protect the elderly from infectious diseases by finding ways to slow or stop the degradation of the immune system. The research results are printed in the current edition of the Journal of Experimental Medicine.
"One of the major components of the immune system are T cells, a form of white blood cell. These cells are programmed to look for certain kinds of disease-causing pathogens, then destroy them and the cells infected by them," said Nikolich-Zugich who also serves as a professor of molecular microbiology and immunology in the OHSU School of Medicine, and is a senior scientist at the OHSU Oregon National Primate Research Center. "Throughout our lives, we have a very diverse population of T cells in our bodies. However, late in life this T cell population becomes less diverse, potentially resulting in a higher level of susceptibility to disease. We think we have found one of the key reasons behind this age-related susceptibility."
Specifically, in old age, the number of CD8 T cells diminishes. CD8 T cells have two functions: to recognize and destroy abnormal or infected cells, and to suppress the activity of other white blood cells to protect normal tissue. The scientists believe that late in life a different kind of CD8 T cell is increasingly produced by the body. These cells, called T cell clonal expansions (TCE), are less effective in fighting disease. They also have the ability to accumulate quickly as they have a prolonged lifespan and can avoid normal elimination in the organism.
In the end, these TCE cells can grow to become more than 80 percent of the total CD8 population. The accumulation of this one type of cell takes away valuable space from other cells, resulting in an immune system that is less diverse and thus less capable in effectively locating and eliminating pathogens.
To conduct the research, scientists at the VGTI studied mice, which have immune system function very similar to humans. The scientists found the aging mice to have greater TCE levels than normal mice, a less diverse population of CD8 T cells and reduced ability to fight disease. In addition, the scientists were able to show that increasing TCE cells in a normal, healthy mouse reduces that animal's ability to fight disease.
"While this work is still in the early stages, we think it might be of great value," explained Nikolich-Zugich. "If we can find ways to limit the production of TCE in the aging, we might be able to keep their immune systems strong and better able to fight disease. To provide a real-life example: A flu vaccine shortage like the one we are witnessing might be less concerning if elderly Americans were made less susceptible."
During development the immune system's cells reshuffle an area of DNA in many ways to create T cells that have many different antibody active binding sites to bind to different kinds of antigens (antigens being a large assortment of things including pollen, bacteria, viruses, and yet other potential targets). For each potential invading pathogen we need a small number of immune cells that will recognize it and in response divide rapidly to scale up to meet the challenge of binding to and destroying that invader.
When these TCE cells, which make only a very small number of kinds of antibodies, divide too much they basically squeeze out the other types of T cells. When a pathogen comes along that does not match what the TCE cells can handle then the TCE cells basically refuse to die off to make room for the other types of T cells that can handle the pathogen. This prevents a proper immune response from happening.
In a way the TCE cells pose a problem similar to cancer. They divide too much and squeeze out cells that do necessary jobs. In another way the TCE cells are similar to the T cells that cause auto-immune diseases. They propagate too much to create antibodies that are not needed (in the case of TCEs) or even harmful (in the case of T cells causing auto-immune disorders). It would be interesting to know whether some auto-immune disorders are caused by TCE cells and whether people who suffer from auto-immune disorders have less diverse T cell populations.
In a way this report is good news for people suffering frmo auto-immune disorders because it focuses attention on the need to be able to very selectively eliminate large subsets of immune system cells. A therapy developed to eliminate TCE cells might also be adaptable to use against T cells that are causing auto-immune disorders. Effectively the pool of people who need to have their immune systems selectively pruned back has just gotten a lot larger. This increases the odds of more resources being deployed to develop such therapies.
But what sort of approach will yield a useful way to selectively prune back unwanted T cells? Maybe monoclonal antibodies designed to attack each clone population. That requires being able to characterize each clone population and to find a way make antibodies against it. How hard is all that? I have no idea. Anyone know?
Increasing scientific evidence suggests that prolonged psychological stress takes its toll on the body, but the exact mechanisms by which stress influences disease processes have remained elusive. Now, scientists report that psychological stress may exact its toll, at least in part, by affecting molecules believed to play a key role in cellular aging and, possibly, disease development.
In the study, published in the November 30 issue of Proceedings of the National Academy of Sciences, the UCSF-led team determined that chronic stress, and the perception of life stress, each had a significant impact on three biological factors -- the length of telomeres, the activity of telomerase, and levels of oxidative stress -- in immune system cells known as peripheral blood mononucleocytes, in healthy premenopausal women.
Telomeres are DNA-protein complexes that cap the ends of chromosomes and promote genetic stability. Each time a cell divides, a portion of telomeric DNA dwindles away, and after many rounds of cell division, so much telomeric DNA has diminished that the aged cell stops dividing. Thus, telomeres play a critical role in determining the number of times a cell divides, its health, and its life span. These factors, in turn, affect the health of the tissues that cells form. Telomerase is an enzyme that replenishes a portion of telomeres with each round of cell division, and protects telomeres. Oxidative stress, which causes DNA damage, has been shown to hasten the shortening of telomeres in cell culture.
The results of the study -- which involved 58 women, ages 20-50, all of whom were biological mothers either of a chronically ill child (39 women, so-called "caregivers") or a healthy child (19 women, or "controls") -- were dramatic.
As expected, most women who cared for a chronically ill child reported that they were more stressed than women in the control group, though, as a group, their biological markers were not different from those of the controls. However, in one of the study's key findings, the duration of caregiving -- after controlling for the age of the women -- proved critical: The more years of care giving, the shorter the length of the telomeres, the lower the telomerase activity, and the greater the oxidative stress.
Moreover, the perception of being stressed correlated in both the caregiver and control groups with the biological markers. In fact, in the most stunning result, the telomeres of women with the highest perceived psychological stress -- across both groups -- had undergone the equivalent of approximately 10 years of additional aging, compared with the women across both groups who had the lowest perception of being stressed. The highest-stress group also had significantly decreased telomerase activity and higher oxidative stress than the lowest-stress group.
"The results were striking," says co-author Elizabeth Blackburn, PhD, Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics at UCSF. "This is the first evidence that chronic psychological stress -- and how a person perceives stress -- may damp down telomerase and have a significant impact on the length of telomeres, suggesting that stress may modulate the rate of cellular aging."
The link from mind to body
"Numerous studies have solidly demonstrated a link between chronic psychological stress and indices of impaired health, including cardiovascular disease and weakened immune function," says lead author Elissa Epel, PhD, UCSF assistant professor of psychiatry. "The new findings suggest a cellular mechanism for how chronic stress may cause premature onset of disease. Anecdotal evidence and scientific evidence has have suggested that chronic stress can take years off your life; the implications of this study are that this is true at the cellular level. Chronic stress appears to have the potential to shorten the life of cells, at least immune cells."
While it is not yet clear how psychological stress impacts telomeres, the team suspects stress hormones may play a role.
The next investigative steps
A next step in the research will be determining if prolonged psychological stress has an impact on telomeres in other types of cells, such as cells of the lining of the cardiovascular system.
The scientists also plan to further examine the impact of prolonged psychological stress on immune system cells, which mount the body's healing response to wounds, and defenses against illness. When the immune system needs to rev up, it produces more defense cells, which requires high levels of the telomerase enzyme, in order to maintain telomere length, thus allowing for additional rounds of cell division. The current study suggests that, for people under chronic stress, the telomerase activity of their immune cells might be impaired.
These scientists are now going to conduct a longitudinal study (following the same group of subject for years while repeatedly testing them) to prove that stress really does accelerate aging as measured by telomere length.
For those of you asking "What are telomeres and why are they important?" here is the short version: Telomeres are caps on the ends of chromosomes. They are made up of a very simple repeating sequence of DNA. Every time a cell divides its telomere gets shortened. Eventually the telomere gets so short that somehow as a result the cell can no longer divide or can divide only slowly and with increasing genetic damage.
So how to telomeres get long in the first place if they normally get shorter in all cells that divide? Way back at some step in the creation of an embryo (sorry, I don't know when, maybe when eggs and sperm are made? Or right after fertilization? anyone biologists reading this who know?) the telomerase enzyme gets turned on to lengthen telomeres. After that most (though perhaps not all) cell types do not have active telomerase and when they divide they get progressively shorter telomeres. The shortening of the telomeres serves as one limit on how many times cells can divide.
My guess on the study reported above is that the mechanism of telomere shortening the researchers are observing is that stress causes certain classes of cells to divide more rapidly. Keep in mind that not all cells divide. For example, most nerve and heart cells are what are called post-mitotic. They no longer go through mitotic cell division. But skin cells and the various types of adult stem cells divide. One major cause of aging is that adult stem cell reservoirs throughout the body go through so many divisions that their telomeres get too short and they can't divide very well to provide cells to do repair.
Evidence has previously been found linking telomere length to mortality risk. The length of telomeres in endothelial progenitor cells (a type of adult stem cell) is linked to increased risk of cardiovascular disease. So those cells would be logical candidates to check for telomere length in women who have been under sustained stress.
You might think that lengthening telomeres would be a great way to rejuvenate cells. Well, like so many things in life, it depends. In order for cancer cells to become cancerous one of the mutations that helps them divide better is to turn on telomerase (an enzyme that lengthens telomeres) so that telomere length won't be an obstacle to the cancer's growth. A blanket lengthening of all the telomeres of all the cells in your body (say by a gene therapy yet to be developed) would probably substantially increase your risk of cancer. Of course, for someone who is about to die from some non-cancer disease telomere lengthening might increase their lifespan by enabling adult stem cells and other cells to divide and repair damaged tissue.
Telomere lengthening techniques usable in cell culture have been developed. But the use such techniques on adult stem cells removed from your body would probably best be done in combination with genetic testing and selection processes (still to be developed) that would assure these stem cells do not already have genetic mutations that increase the risk of the cells going cancerous. Aubrey de Grey proposes reseeding adult stem cell reservoirs with cells that have lengthened telomeres. Aubrey goes so far as to argue that the replacement stem cells should have their telomerase enzymes removed entirely in order to provide a limit to cancer cell replication. Evidence from mice shows that bone marrow stem cell replenishment reduces the risk of atherosclerosis.
My advice: Avoid stress. Also, support scientific research into rejuvenation. Your telomeres are getting shorter every day and that is not good. We need safe rejuvenation therapies to give us young adult stem cells and other cell types.
Plastic surgeon Val Lambros, MD says the major cause of change in facial appearance is loss of fat that causes deflation of the skin in toward muscles and bones.
PHILADELPHIA – To the surprise of many people, the loss of fat and sun exposure play a bigger role than gravity in aging the face, according to a study presented today at the American Society of Plastic Surgeons (ASPS) Plastic Surgery 2004 conference in Philadelphia.
“People make assumptions about how the face ages because when they pull up on their facial skin, they look better,” said Val Lambros, MD, ASPS member and author of the study. “Actually the pull of gravity on facial tissues is not a significant component of facial aging. Instead, other factors, like the loss of facial fat and sun damage are more contributory in the complex process of aging.”
In addition, the nature of facial skin changes over time becoming thinner, most notably around the eyelids. These changes are often accelerated by sun exposure, which damages the skin.
“Plastic surgeons rejuvenate the aging face by pulling up and tightening the tissue, but treatment also requires a balance between tightening tissue and replacing loss facial fat with wrinkle fillers,” said Dr. Lambros. “The key is knowing how much of each to do.”
Surprisingly, he said, only a few features shifted over time. The subjects' brows fell slightly and their upper lips thinned. Their jowls became more prominent, but they expanded rather than dropped. Every other feature in the photographs remained perfectly still.
Subcutaneous fat injections are now part of the repetoire of plastic surgeons. However, fat injections and collagen injections typically last only several months.
Results: The duration of the fat injections varies significantly from patient to patient. Though some patients have reported results lasting a year or more, the majority of patients find that at least half of the injected fullness disappears within 3-6 months. Therefore, repeated injections may be necessary.
What is needed is the ability to move intact fat cells in a way that allows a higher percentage of them to survive at the transplanted location. One report I found on injection of fat into penises to make them thicker (really!) mentions that perhaps 30% of transplanted cells live. So then would several transplants over a period of a couple of years eventually result in a large enough build-up of viable fat cells at the target location that further transplants would not be necessary? Anyone know?
ORONO, Maine – High blood pressure in otherwise healthy adults between the ages of 18 and 83 is associated with a measurable decline in cognitive function, according to a report published today by University of Maine researchers in the pre-publication online edition of the journal Hypertension. The article will appear in the October issue of the printed journal.
While they characterize the decline as “relatively minor and manageable in terms of everyday functioning,” the authors say their findings underscore the importance of treatment for high blood pressure. In the study, younger individuals (18-47) performed at a higher level on cognitive function tests than did older individuals (48-83), but they, like older individuals, showed blood pressure-related decline in cognitive function over time.
There is a larger lesson here for younger people because this study fits into a larger pattern. Lots of factors that increase the risk of heart disease, cancer, cognitive decline, and other symptoms of aging characteristic of later life also degrade performance earlier in life. For example, exercise boosts cognitive function at any age. So lack of exercise when one is in one's 20s or 30s is reducing one's cognitive function below what it otherwise would be at those ages. It is never too early to start getting lots of exercise or eating an optimal diet.
An IQ test was used to show the decline in cognitive function due to high blood pressure.
Subjects in the study exhibited a normal range of cognitive functioning, as determined by the Wechsler Adult Intelligence Scale (WAIS). People suffering from dementia, diabetes, psychiatric illness, alcoholism, drug abuse or stroke were excluded.
In tests of four major areas of mental function, the researchers found that measurements of problem solving abilities under time constraints showed a statistically significant association with blood pressure in younger and older adults, aged 18-83.
Unfortunately, just as a rising rate of child obesity is raising the risk of heart disease and of insulin-resistant diabetes rising prevalence of obesity is also increasing the incidence of early onset high blood pressure.
"What we're finding is that with the current epidemic of overweight and couch-potato children, a higher percentage than ever before are in the hypertensive range," said Dr. Julie R. Ingelfinger, a pediatrics professor at Harvard Medical School.
Obesity has got to be the biggest health problem in the industrialized nations. It increases the risk of many different diseases. Obesity not only increases the risk of cancer but it also has recently been shown that the risk of dying from breast cancer among those who are diagnosed is greater if one is overweight. So obesity makes cancer not only more likely to happen but more deadly for those who get it.
They found that taking beta-blockers together with thiazide diuretics, which protect against bone loss, was linked to a reduced risk of fracture of 29%.
Using beta-blockers alone for around six months was linked to a 23% reduced risk. Taking thiazides alone was associated with a 20% risk.
Quite a large body of research literature is building in support of the idea that chronic inflammation is a major cause of many degenerative diseases. One of the causes of chronic inflammation is obesity.
In research published in the Sept 21 issue of Circulation, the researchers show for the first time that circulating mononuclear cells -- the body's monocytes (the largest type of white blood cell) and lymphocytes -- exist in a proinflammatory state in obese persons known to be at increased risk of developing diabetes, heart disease or both.
"These cells are creating a lot of nuisance in the obese," said Paresh Dandona, M.D., Ph.D., head of UB's Division of Endocrinology, Diabetes and Metabolism and senior author on the study. "They enter the artery and set up atherosclerosis. They activate fat cells to produce more proinflammatory factors. They interfere with insulin signaling, causing insulin resistance. They even enter the brain."
Husam Ghanim, Ph.D., research associate, is first author on the study.
The good news, said Dandona, is that, based on these findings, the status of mononuclear cells from one blood sample could serve as an easy early-warning system for the risk of developing insulin resistance and circulatory problems.
The research was conducted using fasting blood samples from 16 normal-weight subjects with an average body mass index (BMI) of 22.6 and from 16 obese subjects with an average BMI of 40. All participants had similar glucose levels and were taking no anti-inflammatory medication. The research was conducted at the Diabetes-Endocrinology Center of Western New York located in Kaleida Health's Milliard Fillmore-Gates Hospital.
Mononuclear cells were isolated, and proinflammatory and anti-inflammatory factors within the nucleus and the cell were assayed. The researchers also calculated an insulin-resistance index for each participant, using a standard formula.
Results showed that measures of proinflammatory factors were significantly higher in blood samples from obese subjects than the average weight subjects, while levels of factors that normally inhibit inflammation were significantly lower.
"This proinflammatory state may contribute to insulin resistance," said Dandona, "because the cytokines produced may interfere with insulin action." The index of insulin resistance in the obese subjects was nearly three times higher, on average, than that of the normal subjects, findings showed.
Lose excess weight to lower your level of body-wide inflammation and you will live longer as a result.
The randomized trial was conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome. Patients in the intervention group (n=90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n=90) followed a prudent diet (carbohydrates, 50 percent-60 percent; proteins, 15 percent-20 percent; total fat, less than 30 percent).
The researchers found that after 2 years, patients in the Mediterranean diet intervention group had significant decreases in body weight, blood pressure, levels of glucose, insulin, total cholesterol, and triglycerides and a significant increase in levels of high-density lipoprotein cholesterol, all of which were greater than those recorded in the control group. Serum concentrations of interleukins 6 (IL-6), 7 (IL-7), and 18 (IL-18) and high-sensitivity C-reactive protein (hs-CRP) were significantly reduced in patients in the intervention group compared with those in the control group. Endothelial function score improved in the intervention group but remained stable in the control group. Forty patients consuming the intervention diet still had features of the metabolic syndrome, compared with 78 patients consuming the control diet. Participants who followed the intervention diet showed a reduction in the number of the components of the syndrome such that the overall prevalence of the metabolic syndrome was reduced by approximately one half.
You can also read the abstract of the Journal of the American Medical Association paper of the previous report.
Elevatation of inflammation marker high-sensitivity C Reactive Protein (hs-CRP) correlates with greater arterial plaque build-up and therefore greater risk of heart disease and other circulatory ailments.
The study of 386 Olmsted County, Minn., residents used transesophageal echocardiography (TEE) to obtain high-quality images of the lining of the aorta, the main artery through which the heart pumps blood to the body. TEE images are clearer than traditional echocardiograms because they come from an ultrasound probe inserted down the throat. This enables imaging of the heart and major blood vessels without interference from the ribs and chest wall.
The researchers found partial blockages, called atherosclerotic plaques, in the aortas of 69 percent of the study subjects, whose median age was 66. The level of high-sensitivity C-reactive protein (hs-CRP), a marker in the bloodstream that indicates inflammation, was the single factor most closely associated with the presence of plaques and their severity.
Emotional states have a large influence on blood levels of C Reactive Protein and the risk of circulatory and heart-related ailments. Anger and depression increase the risks of heart disease .
In earlier studies, Suarez has shown that people who are prone to anger, hostility and depressive symptoms respond to stress with increased production of the stress hormone norepinephrine. Scientific evidence suggests that an increase in this stress hormone activates the inflammatory arm of the immune system and triggers the expression of genes that cause chronic, low-grade inflammation. This inflammation is characterized by high levels of CRP, he said.
"Individuals with these psychological attributes may evaluate their environment in a cynically hostile manner, and thus respond with greater anger, which is often accompanied by mild to moderate symptoms of depression," said Suarez. "These psychological attributes tend to cluster within the same individual, and the clustering of attributes may produce even greater risk than any single trait alone."
Suarez said the levels of depressive symptoms and angry/hostile moods necessary to raise CRP do not constitute psychiatric conditions. "That is, you don't have to be clinically depressed or have extreme and frequent bouts of anger to show higher levels of CRP," he said.
In the Duke study, 121 healthy men and women were asked to complete standard personality questionnaires in which they described their psychological attributes, including anger, hostility and depression. The volunteers did not have any pre-existing conditions -- such as smoking, high blood pressure, diabetes or heart disease -- that would predispose them to having high CRP levels. High-sensitivity blood tests were then conducted to measure CRP levels.Respondents who were prone to anger, had high hostility levels, and showed mild to moderate symptoms of depression had two to three times higher CRP levels than their calmer counterparts. The more pronounced their negative moods, the higher CRP levels they had, the study showed.
The highest levels of CRP were in the range of 1.7 mg/L to 3.0 mg/L. While these levels are still considered relatively low – fever, an active infection, or physical trauma is associated with CRP levels above 10.0/mg/L –CRP levels in this range are associated with a moderate to high risk of heart attacks and strokes, said Suarez.
Stay skinny. Eat great food. Also, be careful with your thoughts since they have a lot of impact upon your body. Avoid anger and depression. Plus, since exercise lowers inflammation markers and brightens the mood working out is good for your mental and physical health.
DALLAS – Sept. 14, 2004 – Prolonged and sustained endurance training prevents stiffening of the heart, a condition associated with the onset of heart failure, according to researchers at UT Southwestern Medical Center at Dallas.
The researchers also report that a sedentary lifestyle, in addition to aging, puts older people at risk for heart failure, the leading cause of hospitalizations for patients over 65 and a condition that affects eight out of every 1,000 people older than 70.
Their findings are available online and will be published in the Sept. 28 print edition of Circulation.
"It appears that lifelong exercise training completely prevented the stiffening of the heart muscle that has been thought to be an inevitable consequence of aging. We found that it is aging in addition to being sedentary," said Dr. Benjamin Levine, professor of internal medicine and senior author of the study.
"If people can train and sustain it, a huge impact will be made on one of the biggest scourges of the elderly, which is heart failure with a normal ejection fraction, also called 'diastolic heart failure'. The overall health of the population would radically improve if a larger number of people would make exercise a part of their daily life."
About 40 percent of all hospitalizations for heart failure in patients 65 and older are due to diastolic heart failure, a condition in which the heart appears to pump normally. It appears to occur as a result of stiffening of the heart muscle, causing excess fluid to accumulate in the lungs, feet, ankles and legs.
The researchers measured the function and compliance of the left ventricle (the heart's main pumping chamber) in the study participants. Twelve healthy but sedentary seniors (all about 70 years old), 12 Masters athletes (average age of 68) and 14 young, sedentary controls, (average age of 29) were tested. Six of the Masters athletes, who participate in events from swimming to track, were nationally ranked competitors and six were regional champions. Sedentary participants had not engaged in regular endurance exercise throughout their life.
The researchers tested whether left ventricular compliance decreased with aging alone, or if physical inactivity contributed equally to this process.
"We found that the older, sedentary individuals' hearts were 50 percent stiffer than the Masters athletes, which we expected," said Dr. Levine, medical director of the Institute for Exercise and Environmental Medicine, a collaboration between UT Southwestern and Presbyterian Hospital of Dallas. "But what we didn't expect was that the hearts of these senior athletes were indistinguishable from those of the healthy younger participants.
"That specific finding led us to conclude that a sedentary lifestyle is associated with a decline of ventricular compliance and prolonged, sustained endurance training preserves ventricular compliance and may reduce the high incidence of heart failure in the elderly."
Exercise will provide a large benefit even if started later in life.
Dr. Levine and his collaborators have already designed an endurance-training program for several of the elderly, sedentary study participants, which has already yielded dramatic results.
"About two-thirds of the sedentary, elderly participants have trained for a year and there is already improvement in their cardiac compliance. Their hearts are more muscular and more flexible," Dr. Levine said.
A sedentary lifestyle is detrimental to one's health, but starting and sticking with an endurance-training program plays a major role in reversing the damage done to the heart, even if that program is initiated later in life, he added. Most of the Masters athletes were not elite athletes when they were younger, Dr. Levine pointed out. In fact, most of them did not start training until they were in their 30s.
Exercise also raises blood HDL cholesterol levels. So you can also reduce your risk of artery clogging by exercising. My advice: Get a dog that likes to run and obey his daily entreaties to get out there and run like a dog.
Dr. Leonid A. Gavrilov and Dr. Natalia S. Gavrilova have a new article out in the IEEE Spectrum on their reliability engineering approach to understanding aging.
If only we could maintain our body functions as they are at age 10, we could expect to live about 5000 years on average. Unfortunately, from age 11 on, it's all downhill!
The problem is that our bodies deteriorate with age. For most of our lives, the risk of death is increasing exponentially, doubling every eight years. So, why do we fall apart, and what can we do about it?
They go on to explain how engineering reliability theory can be applied to understanding how humans age and die. One of their conclusions is the same position argued for by rejuvenation advocates: we need to develop the ability to grow replacement parts and to do more kinds of repairs.
Their point that we start increasing our risk of dying of aging from about age 11 is demonstrated by a recent study led by Dr Faisal Khan of the University of Dundee in the UK. Dundee and colleagues found that children as young as 11 years old already show signs of endothelial cell dysfunction that will contribute to the development of heart disease and other circulatory diseases.
“This is the stage of life where changes to a person’s body are potentially reversible,” says lead researcher Faisal Khan at the University of Dundee, UK. “If you leave it until their 30s or 40s, it is much harder.”
Khan and his colleagues studied the lining of tiny blood vessels, or endothelium, in 158 Scottish children, aged 11 to 14. Within this group, 20% of children showed impaired endothelial activity.
In some children capillaries failed to expand in response to drug exposure.
The researchers rubbed a drug through their skin to make their blood vessels expand. The vessels were then monitored using a laser.
In about 20 per cent of children, the tiny capillaries and arteries failed to expand, suggesting that the cells lining the vessels, a layer called the endothelium, was damaged. Endothelial cells control a vessel's ability to contract and dilate.
Problems in the cells that make up endothelium can lead to progressive hardening and narrowing of blood vessels, called atherosclerosis, which can ultimately lead to cardiovascular diseases.
The rate of malfunction of epithelial cells is higher in obese kids. Even in youth bad diets begin the process of accumulation of aging damage. It is never too soon to start eating a healthful diet.
How many defects we are born with determines how much redundancy we have to start out with in all our bodiy systems. We all start out with a different total number of microscopic errors in our bodies at birth. From that point on the rates at which we accumulate more damage varies from person to person and under different living conditions. There is some amount of randomness as to where the damage occurs.
We are actually better off if the damage accumulation is more evenly spread. If the damage accumulation is concentrated in a sinlge essential component then that component will fail sooner and kill us sooner.
We need better ways to slow damage accumulation. But even more so we need techniques for doing repair and replacement. Cell therapy, growth of replacement organs, and techniques for getting rid of accumulated junk are just a few of the several Strategies of Engineered Negligible Senescence that could fix our accumulated damage and restore redundancy to our aging body parts.
ROCHESTER, Minn. -- Weight gain and bone thinning may seem to be natural complications of aging in humans and mice. Now, Mayo Clinic researchers have discovered a genetic basis for this physical decline -- and have suggested that “silencing,” or turning off a specific gene complex, may halt weight gain and control bone loss. The team found laboratory mice without this gene function have 70 percent less body fat and exhibit the dense bones and lean bodies of young mice.The researchers dub the mice “Adonis,” after the youth in Greek mythology who had an ideal, youthful physique. Their report appears in the August issue of FASEB Journal published by The Federation of American Societies for Experimental Biology. The work connects the function of genes important in the immune response with processes of physical development and aging. This functional linkage between the immune system, and on body plan and aging, was first described in fruit flies through the study of a gene called Toll. The mouse and human version of Toll is TLR4, which stands for “Toll-like Receptor 4.”
Mutations in either of two genes prevented much of age-related bone loss and increase in fat.
The group of mice under investigation was genetically the same as the healthy control mice except that they had mutations in TLR4 or in a signaling gene it needs called CD14. Bone density, bone mineral content, bone area, total body mass, fat body mass and fat-free body mass were tested and analyzed by computer with specialized software. Bone growth in the legs was evaluated. Physical activity was tracked with a computerized observational system. Food and water were provided throughout the experiment. Muscle mass was determined, but muscle strength was not checked. Eighteen tests were given to all mice to periodically check for bacteria, viruses and toxins.
Researchers found that the mutant mice whose TLR4 was silenced had:
- Greater bone mineral content at 20 weeks of age compared to normal mice -- and that this relationship increased as both groups aged.
- Larger bones at 20-24 weeks of age.
- 70 percent less body fat than the control group as they grew and aged.
It would be interesting to know whether these mice will live any longer or shorter than wild type mice.
It might then seem logical for life extension advocates to advocate the development of drugs to silence TLR4 (perhaps based on DNA anti-sense technology or RNA interference technology). But keep in mind that TLR4 plays an important role in spurring the immune response to dangerous blood infections.
Immunologists think that stimulation of TLR4 is a crucial first step in mounting an immune response in mice and in humans. TLR4 usually responds to endotoxins, which are carried by the bacteria that cause sepsis, a dangerous blood infection. Sepsis occurs in 400,000 people in the United States annually; as many as half may die. Because of its seriousness, Mayo Clinic immunology researchers were interested in understanding the mechanism of sepsis.
Perhaps this can be finessed somehow. If compounds that could act in place of TLR4 could be found then those compounds could be delivered to patients whose own TLR4 genes have been suppressed by a DNA anti-sense drug. Alternatively, perhaps a drug can be developed that will suppress TLR4's effects on fat cells or bone cells (aside: does TLR4 down-regulate osteoblasts or up-regulate osteoclasts?) without interfering with immune response.
Another possibility is to suppress whatever factors might be up-regulating TLR4 in aging bodies. But my guess is that the most likely factor for the cause of TLR4 expression in old folks is an accumulation of damage that causes an inflammation response. Generally speaking, as people age more of their inflammation and repair genes are activated. Possibly we can selectively suppress subsets of those genes to achieve some slowing of aging. But what we really need to do most of all is to be able to repair all the things that are breaking. Regular readers know that this means we need to develop therapies based on SENS (Strategies for Engineered Negligible Senescence).
Calorie Restriction (CR) diets that reduce calories about 35% below normal have been shown to increase average life expectancy across a large assortment of animal species (though the longevity enhancing effect of CR has not yet been confirmed in humans). The life extending effect of CR has been the subject of a great deal of research attention as researchers have sought to find compounds that will throw the body into a metabolic state that is like the CR state. The hope is that a drug could provide the same life extending effects but without the need to feel perpetually hungry and to look gaunt.
Some researchers have been comparing the pattern of gene expression found in mice on CR diets with the patterns of gene expression found in mice given a variety of drugs. Some already used drugs may induce a metabolic state that will extend life expectancy by the same mechanism that CR diets extend life expectancy.
Investigators from an international consortium of research institutes, including the Johns Hopkins Bloomberg School of Public Health, have identified compounds that mimic the effects of a low-calorie diet without changing the amount of essential nutrients.
The lack of PPARalpha prevented some of the changes in metabolism normally seen on a CR diet.
Lead author, J. Christopher Corton, PhD, with ToxicoGenomics in Chapel Hill, NC, examined the genetic changes that occur during calorie restriction in mice that were fed a diet for one month containing about 35 percent fewer calories than a normal diet. He explained that these genetic changes, which are referred to as a transcript profile, can be used like a bar-code to distinguish a unique profile from other genetic changes that occur in the body. The researchers compared the profile of calorie restriction with the profiles produced by compounds known to have some properties similar to calorie restriction, including the ability to suppress factors that lead to a number of diseases.
The compounds that shared the greatest similarities in the bar codes included those that have activity toward receptors of interest to the pharmaceutical industry. The receptors include those that are targeted by drugs used to treat high cholesterol and triglyceride levels. One of the receptors, called PPARalpha, is a target for drugs that are currently used to treat high cholesterol and triglyceride levels in people at risk for heart disease.
The investigators also compared responses in normal mice to mice that lack a functional PPARalpha to determine if PPARalpha was directly involved in any of the responses that are induced by calorie restriction. They found that the PPARalpha-mutant mice lack many of the characteristics of calorie restriction, including changes in genes that may play important roles in heart disease and cancer. Calorie restriction is also known to protect animals from chemical exposure, and the investigators found that the protection afforded by calorie
It may turn out to be the case that some existing drugs that target PPARalpha are already benefitting their users by inducing a metabolic state that is similar to the state induced by calorie restriction.
The press release above does not indicate which cholesterol lowering drugs the researchers were using. However, my suspicion is that they were using statin drugs since statin drugs are known to activate PPARalpha. Well, Lipitor and Crestor users might be benefitting from CR-like effects on their bodies.
ITHACA, N.Y. -- A study by researchers at Cornell University suggests that higher-than-normal amounts of a selenium-containing enzyme could promote type 2 diabetes. The researchers found that mice with elevated levels of the antioxidant enzyme develop the precursors of diabetes at much higher rates than did control mice.
Selenium, a common dietary supplement, is an antioxidant, materials that help mop up harmful free radicals, molecules that can damage cell membranes and genetic material and contribute to the development of cancer and heart disease. Many of the benefits of selenium are related to its role in the production of glutathione peroxidase (GP), an antioxidant enzyme that helps detoxify the body.
"Although free radicals are known to be harmful and antioxidants helpful, our study suggests that we actually need some free radicals to regulate insulin sensitivity," says Xingen Lei, associate professor of animal science at Cornell and an author of the study, published in the June 15 issue of the Proceedings of the National Academy of Sciences , and now available online. The lead author is James McClung, who received his Ph.D. from Cornell this spring and is now a diabetes researcher at a U.S. Army laboratory in Boston.
McClung notes that high levels of GP appear to promote diabetes by mopping up too many free radicals, which are needed to help switch insulin signaling on and off in glucose (blood sugar) metabolism.
"Most people believe that both selenium and the selenium-containing enzyme GP are good for health by protecting cells and tissues from oxidation. However, this study suggests that they are a double-edged sword," says Lei. "Antioxidants can be harmful by neutralizing too many free radicals and interfering with insulin signaling, which results in promoting obesity, insulin resistance and possibly diabetes."
He points out that these findings are consistent with a recent study of pregnant women that reported on a link between high levels of GP, insulin resistance and gestational diabetes.
"Before people blindly supplement their diets with antioxidants, such as selenium and vitamins E and C, more research is needed," he concludes. Next, Lei plans to put the obese mice from this study on a diet to see if weight loss and fat loss can prevent or improve the mice's insulin sensitivity.
Diabetes, both type I and type II, effectively accelerates aging in a number of ways. Therefore anything that might contribute to the incidence of type II diabetes should be seen as a potential aging accelerator. Obesity is the largest risk factor for type II dabetes and the rising incidence of obesity is contributing to a rising incidence of type II (so-called adult onset or insulin insensitive) diabetes.
What is unanswered by this current study is whether a higher level of selenium in the diet or through supplementation will cause an unhealthily high level of glutathione peroxidase (GP) activity. Maybe not. In this experiment the scientists made the mice produce more GP. Just taking more selenium may not up GP activity to a level that will be unhealthy since the supply of GP will become a rate-limiting factor once all GP enzymes have selenium in their active centers. Still, the fact that excessive antioxidant activity can contribute to type II diabetes is important news.
Denman Harman, the original developer of the free radical theory of aging, has argued that, yes, there is such a thing as too much antioxidants. He found that taking too much antioxidant vitamins made him feel sluggish. This makes sense. Starting in the 1970s scientists have discovered that free radicals to be involved in an increasing number of signalling pathways in the body. If all our free radicals were quenched by extremely powerful antioxidants we'd literally die and rather quickly.
There are very likely optimal levels and ratios of antioxidant vitamins and minerals. But unfortunately at this point we do not know what those levels are. This latest study suggests that useful insights could be gotten from the measurement of precursors to type II diabetes in animals and people taking large amounts of various types of antioxidants.
Could mice hold the secret to longer life?
Scientists from the University of Aberdeen, the Aberdeen-based Rowett Research Institute and the Medical Research Council (MRC) in Cambridge have made a major breakthrough in understanding how metabolism affects lifespan.
In a seven-year study of mice they found that those with the highest metabolic rate lived the longest, raising the prospect that the effect could be mimicked in humans.
Scientists have long thought that a high metabolic rate was linked to a shortened life-span. The present discovery turns this century old belief on its head and changes dramatically our understanding of the regulation of life-span.
Metabolism is the means by which nutrients are broken down to smaller building blocks and chemical energy, which are used to make new body materials and to do work.
The researchers discovered that the most metabolically active 25% of the mice studied, far from having shorter life-spans, in fact lived 36% longer than the least active. If the same effects are mimicked in humans then the finding would imply that a higher metabolic rate could add an extra 27 years to the average human lifespan.
When the muscles of the most metabolically active mice were examined, they were found to contain factors that increased their metabolism by making it less efficient.
Although the scientists do not yet fully understand how these factors work, it is suspected that while the make the metabolism less efficient, on the positive side they reduce the generation of toxic by-products called "oxygen free radicals".
Blondie has assured us "Live fast because it won't last". But the leader of this research team says live fast to die old.
"We are really excited by this finding," said Professor John Speakman, leader of the research team. "The result is striking: living fast means dying old."
I asked U Cambridge biogerontologist Aubrey de Grey for some comments on this report and here is his email response: (with his permission)
It's a fine study, but not as much of a revision of existing thinking as the press reports make out. The investigators are talking about efficiency of conversion of proton gradient into ATP, as opposed to conversion of oxygen into water. In other words, the long lived animals are expressing uncoupling proteins that make their mitochondria generate more than the usual amount of heat and less than the usual amount of ATP. A side-effect of this is that the proton gradient is lower, which allows electrons to slide along the electron transport chain more quickly, getting stuck less of the time at points where they can fall out and make ROS, so the ROS production is lower.
Aubrey's reference to ROS is to Reactive Oxygen Species which are damaging molecules generated as a side-effect of oxidation of sugars to make chemical energy. This happens in mitochondria which are organelles found inside of cells where sugars are broken down to create chemical energy molecules.
This latest result is not really unexpected given what is already known about mitochondrial metablism and free radical generation. Still, it is a nice piece of work that underlines the importance of mitochondria in cellullar aging.
These longer lived mice probably have to eat more calories in food to stay alive because a smaller fraction of the sugar they break down gets converted into useful chemical energy in the form of the energy carrying molecule ATP (Adenosine TriPhosphate). The mitochondria make the chemical energy carrying molecule ATP from ADP (Adenosine DiPhosphate) by using the energy unleashed by breaking down sugar to add a phosphate to ADP. This reaction requires a proton gradient but making that proton gradient steep also causes the mitochondria to generate more free radicals that inflict the damage which accumulates to cause aging.
This report is not the only recent piece of evidence for the theories that mitochondrial free radical generation is a major cause of aging. Also read my post Mice With Defective Mitochondrial DNA Repair Gene Age More Rapidly.
We can hope for treatments that will lower the rate at which mitochondria generate free radicals. However, what we need even more is the ability to repair the accumulated damage. We need to develop the means to grow replacement organs, control stem cells, deliver gene therapies, and other Strategies for Engineered Negligible Senescence.
Scientists at the Karolinska Institute have found that changes in the "powerhouse" of cells, the mitochondria, play a key role in aging. The findings are being published in this week's issue of the journal Nature.
Mitochondria, which provide energy to cells, have their own set of DNA. Mutations of mitochondrial DNA increase with age, but until now no one knew whether this is a result of aging or a cause of aging. New research findings now indicate that the latter is the case.
Mice with a deficient capacity to correct mutations in mitochondrial DNA acquired an increased number of mutations and proved to age considerably earlier than normal. They lived an average of 10 to 12 months compared with the normal 2 or 3 years. These mice also developed several typical signs of premature aging, such as osteoporosis, weight loss, hair loss, anemia, reduced fertility, and heart muscle disorders.
The findings reveal fundamental biological mechanisms that lie behind the aging process. This knowledge paves the way for the possibility of slowing down aging and treating pathological changes that arise in connection with aging by protecting mitochondrial DNA from damage.
Mitochondria are organelles that exist inside all eukaryotic cells (most complex life forms including humans have eukaryotic cells) and function to break down sugars to produce energy. Mitochonida have their own DNA for a small subset of their proteins. The Swedish team introduced a mutation to break a repair mechanism for the DNA in mitochondria in order to study how important accumulation of damage to mitochondrial DNA is to the overall rate of aging. The results suggest that damage accumulation to mitochondrial DNA is as important as some scientists have argued for years.
Starting at young adulthood (24 weeks), the mice began to show symptoms of premature aging, including weight loss, hair loss, curvature of the spine, osteoporosis, and enlargement of the heart. They lived an average of 48 weeks, and all had died by the age of 61 weeks. Normal lab mice can live up to two years. Designing the experiment and carrying it out took a painstaking four years, Larsson said. ''I now know why no one had done it [before]," he said.
Why does the accumulation of mitochondrial DNA damage accelerate aging? One obvious possibility is that the DNA damage knocks out genes needed for energy production and hence cells begin to malfunction due to a lack of energy. But another quite plausible possibility is that the mutations knock out steps in sugar metabolism in a way that leads to the generation of lots of free radicals. In this model (suggested by Aubrey de Grey - more about him below) the cells that have defective mitochondria become toxic free radical generators for all the cells around them. In essence, a fairly small number of cells become mini-toxic waste sites. Someone call in the Environmental Protection Agency. This sort of thing should be forbidden by tough pollution law enforcement.
University of Cambridge biogerontologist Aubrey de Grey argues that the presence of 13 of the mitochondrial genes actually in the mitochondria makes those genes something akin to an Achilles Heel for human aging. These 13 genes are vulnerable to free radical damage from free radicals generated as a side effect of the main purpose which mitochondria serve breaking down sugars for energy. Aubrey argues that development of gene therapy to move mitochondrial genes into the nucleus could remove a major cause of aging my protecting those genes from the free radicals generated by breaking down sugars for energy.
The mitochondrion is therefore a really essential part of the cell. Lots of other parts of the cell are essential too, though, so why have a whole SENS page on it? The answer in: unlike any other part of the cell, mitochondria have their own DNA. This means that they can stop working as a result of mutations. Because the DNA is in a different place than the rest of the cell's DNA (which is in the nucleus), we need a different system to combat the inevitable accumulation of such mutations.
As usual, we're lucky - evolution has done the hardest part of this for us already. Mitochondria are very complex -- there are about 1000 different proteins in them, each encoded by a different gene. But nearly all of those genes are not in the mitochondrion's DNA at all! -- they are in the nucleus. The proteins are constructed in the cell, outside the mitochondrion, just like all non-mitochondrial proteins. Then, a complicated apparatus called the TIM/TOM complex (no kidding...) hauls the proteins into the mitochondron, through the membranes that make its surface. Only 13 of the mitochondrion's component proteins are encoded by its own DNA.
This gives us a wonderful opportunity: rather than fixing mitochondrial mutations, we can obviate them. We can make copies of those 13 genes, modified in fairly obvious ways so that the TIM/TOM machinery will work on them, and put these copies into the chromosomes in the nucleus. Then, if and when the mitochondrial DNA gets mutated so that one or more of the 13 proteins are no longer being synthesised inside the mitochondria, it won't matter -- the mitochondria will be getting the same proteins from outside. Since genes in our chromosomes are very, very much better protected from mutations than the mitochondrial DNA is, we can rely on the chromosomal copies carrying on working in very nearly all our cells for much longer than a currently normal lifetime.
Aubrey has repeatedly argued for funding of experimental work to move genes into the nucleus of a mouse cell to then be used to clone and raise mice that have all their mitochondrial genes in their nuclei. The effect might be the opposite of the experiment reported above. Rather than shortening life the mice might live much longer. Such a result would lend further support for the argument that mitochondrial DNA gene therapy should be developed as a rejuvenation technique.
Is the movement of mitochondrial genes into the nucleus doable? In a debate from November 2003 with Richard Sprott of the Ellison Medical Foundation Aubrey pointed out that in a yeast strain a single mitochondrial gene was moved into the nucleus 15 years ago.
The third thing we have to fix is what are called mitochondrial mutations. Mitochondria are special machines in the cell that have their own DNA. They only encode thirteen proteins of their own. All the other proteins that make up the very complicated mitochondria come from the nucleus. So the way to obviate, rather than eliminate, mitochondrial mutations with respect to aging is to make copies of these genes and put them in the nucleus, suitably modified so that they still work.
That sounds pretty damned ambitious, just said boldly like that. Right up until you hear that it was actually done successfully fifteen years ago—only for one of those thirteen genes, and only in yeast, but it was done and there has been more progress in mammalian cells with two more of those proteins in the past couple of years. So we are moving fast here.
This latest report provides support for the camp that argues for the development of gene therapies to repair mitochondrial DNA damage as a method to roll back aging and rejuvenate the body. See Aubrey's publications page and the section Obviation of mitochondrial mutations for more on the subject of what to about mitochondrial DNA damage accumulation as a cause of aging.
Now researchers have found that neophobic rats die an average of three months younger than their outgoing brothers — equivalent to ten years shaved off a human life1.
"It shows we need to consider personality traits and behavioural styles when trying to understand physiological mechanisms of health," says Sonia Cavigelli at the University of Chicago, Illinois, who conducted the study with her colleague Martha McClintock.
But way back in our evolutionary past the kinds of personality traits that might make us more depressed or anxious or stressed were probably evolutionarily adaptive for some of our ancestors.
"It was the going up and not coming down as fast," McClintock says. She likens it to hearing a sound in the middle of the night. Some people will wait and listen for a few minutes then fall back asleep. Others will worry for hours, alert for another noise.
"What we showed is that they recovered from that response more slowly," she adds. "We correlated that [with] an early death. It really suggests that we need to look at the effect of having a slow recovery to a stressor to being neophobic, where it happens over and over again on a daily basis."
Then do people who fear the new and unknown need to have their personalities modified in order to live longer? It might be possible to block the physiological response without impacting the emotional response. The reason is pretty simple: it may some day to possible to selectively suppress the stress response in the body when the brain becomes fearful. If the stress response could be suppressed then the more neophobic personalities could probably go through life feeling fear or aversion to new experiences with little resulting damage to their bodies.
The mechanism by which the life of the rats are shortened is probably by fear causing the brain to act on the hypothalamus and other glands to cause them to release stress hormones which in turn cause changes that age the body more rapidly. The changes which shorten life expectancy probably include greater production of immune and inflammation responses. Evidence is accumulating for the role of chronic inflammation in the development of a large variety of diseases. Inflammation may also wear out adult stem cell reservoirs by causing more cell division than would otherwise be the case. So the stem cells more quickly reach their limit in the number of times they can divide and once adult stem cells are no longer available to repair injuries the total amount of damage would accumulate more rapidly.
Still, there is an argument to be made for personality engineering in order to reduce the incidence of neurological disorders. For instance, psychological distress appears to contribute to the development of Alzheimer's Disease.
People who are prone to psychological distress are more likely to develop Alzheimer's disease, research suggests.
Rush University in Chicago found people plagued by negative emotions like depression and anxiety were at double the risk of more laid-back individuals.
But is this higher risk the result of emotional states in the brain acting directly on the brain? Inflammation may play an important role in the development of Alzheimer's. Anti-inflammatory drugs may be able to reduce the level of a peptide that is involved in the formation of amyloid plaques that are characteristic of Alzheimer's.
In a new study, researchers suggest that some anti-inflammatories reduce the levels of a protein fragment (or peptide) associated with Alzheimer's by interfering with two proteins that help manufacture the fragment in the first place. The proteins are called Rho and Rock.
The researchers inhibited Rho and Rock in mutant mice and significantly reduced the levels of the most dangerous peptide found in humans, called amyloid-ß-42. Amyloid peptides form the plaques that are a signature of Alzheimer's disease. The findings are reported in Science.
“The take-home message from this study is that if non-steroidal anti-inflammatory drugs are effective, they may be effective through this [Rho-Rock] mechanism,” says Steven M. Paul of Lilly Research Laboratories in Indianapolis, who led the study. “The mechanism may be unrelated to what these drugs do as anti-inflammatories.”
Now at this point you might be thinking the immortal lyric "Don't worry, be happy". But life is never that simple. A little stress may be good for you
EVANSTON, Ill. -- We've often heard that red wine and dark chocolate in moderation can be good for you. Now it appears that a little stress may be beneficial, too.
Northwestern University scientists have shown that elevated levels of special protective proteins that respond to stress in a cell (known as molecular chaperones) promote longevity. Acute stress triggers a cascading reaction inside cells that results in the repair or elimination of misfolded proteins, prolonging life by preventing or delaying cell damage.
The findings are published online today (Dec. 10) by Molecular Biology of the Cell, a publication of the American Society for Cell Biology. The article will appear in print in the journal's February 2004 issue.
"Sustained stress definitely is not good for you, but it appears that an occasional burst of stress or low levels of stress can be very protective," said Richard I. Morimoto, John Evans Professor of Biology, who co-authored the paper with lead author James F. Morley, a graduate student in Morimoto's lab. "Brief exposure to environmental and physiological stress has long-term benefits to the cell because it unleashes a great number of molecular chaperones that capture all kinds of damaged and misfolded proteins."
Update: UCLA researchers have found that shy people infected with HIV do more poorly on anti-retroviral drug treatment than more outgoing and extroverted people. (or here)
"We found a strong linear relationship between personality and HIV replication rate in the body," Cole said. "Shy people with high stress responses possessed higher viral loads."
The researchers were surprised to find that the antiretroviral drugs barely made a dent in the shy patients' disease. Instead of showing lower viral loads, the immune systems of introverted subjects replicated the virus between 10 to 100 times as fast as in other patients.
"Shy patients on drug therapy didn't experience even a 10-fold drop in their viral load," said Naliboff, co-director of the UCLA Center for Neurovisceral Sciences and Women's Health. "Doctors classify that as a treatment failure. The drugs should shrink HIV replication by at least 100‑fold."
"Our findings suggest that high nervous system activity helps the virus continue replicating," Cole said. "Patients with high-stress personalities continued to lose T-cells — even on the best drug therapy available. Stress sabotages their battle against this lethal disease."
"It looks as though sensitive people are simply wired to respond to stress more strongly than resilient people," Naliboff said. "How someone reacts to stress seems to be more important than the stress itself in explaining why one person gets sick and one person doesn't."
"This heightened stress response is the equivalent of waves striking a stone on the beach," Cole said. "One wave won't do much damage. But the constant pounding of waves eventually grinds that stone to sand. That's how continual stress response wears down the immune system."
Previously the UCLA team found that the body under stress releases a chemical called norepinephrine that leaves the T-cells open to infection and accelerates HIV replication. The researchers' next step will be to try and change shy persons' physiologic response to stress using drugs that block norepinephrine's impact on T-cells.
"Our current study suggests that the body's production of norepinephrine during stress makes a big difference in people trying to fight off infection," Cole said.
Note the part about how these UCLA researchers are going to try to block the physiological response that follows from the cognitive response to stressful situations. The ability to block the brain's ability to send the body into a stress state would be useful for healthy people as well since it would slow and delay the development of many degenerative diseases associated with aging. The stress response is an evolutionary legacy that has become maladaptive in modern industrial society.
Anger is another stressor that has harmful effects on the body. Anger and the lack of friends are both risk factors for periodontal disease.
If you constantly exhibit anger and are a social hermit, such stressors might put your oral health at risk, according to a study in this month's Journal of the American Dental Association. Results from the study reveal that men who reported being angry on a daily basis had a 43 percent higher risk of developing periodontitis (gum disease) compared with men who reported seldom being angry, wrote the Harvard University researchers. In addition, men who reported having at least one close friend had a 30 percent lower risk of developing periodontitis compared with those who did not.
The study authors cited stress as being associated with poor oral hygiene, increased glucocorticoid secretion that can depress immune function and increased insulin resistance. All of these mechanisms, they wrote, can potentially increase the risk of developing periodontitis.
Stress, whether caused by fear of the unknown, loneliness, anger, or other factors, is bad for your health and for your life expectancy.
"Although physicians generally consider Alzheimer and Parkinson diseases to be distinct disorders, the two exhibit a lot of overlap both clinically and pathophysiologically," said Jeffery Vance, M.D., director of Duke's Morris K. Udall Parkinson's Disease Research Center and associate director of the Duke Center for Human Genetics. "This study emphasizes the similarity between the two diseases by highlighting a single gene that influences their age of onset."
The team reports their findings in the Dec. 15, 2003, issue (available online Oct. 21) of Human Molecular Genetics and will present the work as a keynote paper at the annual meeting of the American Society of Human Genetics, which will be held Nov. 4-8, in Los Angeles. The major funding for the study was provided by the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the Alzheimer's Association, the Institute de France, and the American Federation for Aging Research.
The team's earlier work identified a broad chromosomal region linked to the age at onset of Alzheimer's and Parkinson's diseases. The new research -- led by Pericak-Vance, Vance, John Gilbert, Ph.D. and Yi-Ju Li, Ph.D., of the Duke Center for Human Genetics and Jonathan Haines, Ph.D., of Vanderbilt University Medical Center -- narrows that region of the genome, which contained many hundreds of genes, to a single gene known as glutathione S-transferase omega-1 or GSTO1.
It is worth noting that glutathione serves as an intracellular antioxidant that gets oxidized in order to reduce free radicals to less harmful forms. It is not at all surprising that a gene playing a role in antioxidant metabolism would turn out to influence age of onset for two different neurodegenerative diseases. A body that expresses a higher level of genes that detoxify free radicals is, all else equal, not going to age as rapidly as one that expresses those genes at a lower level.
An additional analysis involving 1,773 patients with Alzheimer's disease and 635 patients with Parkinson's disease later found that of those four genes, only GSTO1 showed genetic differences associated with age at onset.
"By combining evidence based on gene expression and genetic association, we found a gene that modifies when the diseases start," said Li, the study's first author. "Understanding the role this gene plays in Alzheimer and Parkinson diseases may, in the future, lead to a means to delay the disorders' onset," she added, noting that even a short delay would benefit at-risk patients.
The development of drugs or gene therapies that would up-regulate genes for enzymes that are involved in quenching free radicals might work as an approach for slowing the general rate of aging and delaying the onset of degenerative disorders of the brain and of other parts of the body.