Genetic variation in the DNA of mitochondria – the “power plants” of cells – contributes to a person’s risk of developing age-related macular degeneration (AMD), Vanderbilt investigators report May 7 in the journal PLoS ONE.
Mitochondrial genes are a logical place to expect genetic variants to influence the rate of aging. The mitochondrial DNA (mtDNA) accumulates damage and mtDNA damage is probably a major cause of aging through out the body.
The study is the first to examine the mitochondrial genome for changes associated with AMD, the leading cause of blindness in Caucasians over age 50.
“Most people don’t realize that we have two genomes,” said lead author Jeff Canter, M.D., M.P.H., an investigator in the Center for Human Genetics Research. “We have the nuclear genome – the “human genome” – that makes the cover of all the magazines, and then we also have this tiny genome in mitochondria in every cell.”
Canter teamed with Jonathan Haines, Ph.D., and Paul Sternberg, M.D., experts in AMD genetics and treatment, to examine whether a particular variation in the mitochondrial genome is associated with the disease. The genetic change occurs in about 10 percent of Caucasians, referred to as mitochondrial haplogroup T.
The tiny bit of mtDNA is much more vulnerable to damage because the mitochondria have lots of reactive chemicals in them in the process of getting converted from sugar into more useful forms of chemical energy. Some of those reactive chemicals bump into the mtDNA and cause damage that messes up energy production. But better mtDNA sequences code for mitochondrial enzymes that basically break down the sugar more cleanly with less intracellular pollution by free radicals.
Members of this team have already discovered a few other genetic variants that contribute to AMD risk.
The genetics of AMD has been a “hot” area lately, Canter said. Haines led a team that identified a variant in the Complement Factor H (CFH) gene as accounting for up to 43 percent of AMD. Variations in ApoE2 and a gene called LOC387715 on chromosome 10 have also been linked to the disease, and Haines and colleagues demonstrated an interaction between the chromosome 10 gene and smoking in raising AMD risk.
The current study also examined variation in these nuclear genes in 280 cases and 280 age-matched controls, and demonstrated that the mitochondrial genome variation was independent of the known nuclear factors.
Once cell therapy and gene therapy become practical I want to upgrade various parts of my body with stem cells that will create longer lasting tissue. We should rejuvenate our bodies. But we should also reduce the maintenance intervals. Studies such as the one above point us in the direction of how to make longer lasting components.
Genetic engineering of a mitochondrial gene in mice to generate more heat causes the mice to live longer.
By making the skeletal muscles of mice use energy less efficiently, researchers report in the December issue of Cell Metabolism, a publication of Cell Press, that they have delayed the animals’ deaths and their development of age-related diseases, including vascular disease, obesity, and one form of cancer. Those health benefits, driven by an increased metabolic rate, appear to come without any direct influence on the aging process itself, according to the researchers.
The mitochondria powering the mouse muscles were made inefficient by increasing the activity of so-called uncoupling protein 1 (UCP1). UCP1 disrupts the transfer of electrons from food to oxygen, a process known as mitochondrial respiration, which normally yields the energy transport molecule ATP. Instead, the energy is lost as heat.
“When you make the mitochondria inefficient, the muscles burn more calories,” a metabolic increase that could be at least a partial substitute for exercise, said Clay Semenkovich of Washington University School of Medicine in St. Louis. “There are a couple of ways to treat obesity and related diseases,” he continued. “You can eat less, but that’s unpopular, or you could eat what you want as these animals did and introduce an altered physiology. It’s a fundamentally different way of addressing the problem.”
This result suggests that the development of drugs to cause the same effect in humans might increase human longevity.
This genetic alteration produced many beneficial effects.
In the new study, Semenkovich’s group used these mice to determine whether respiratory uncoupling in skeletal muscle—a tissue that adapts to altered heat production and oxygen consumption during exercise—can affect age-related disease. They found that animals with increased UCP1 only in skeletal muscle lived longer. Altered female animals also developed lymphoma, a type of cancer that originates in white blood cells called lymphocytes, less frequently. In mice genetically predisposed to vascular disease, the increase in UCP1 led to a decline in atherosclerosis in animals fed a “western-type” high-fat diet. Likewise, mice predisposed to developing diabetes and hypertension were relieved of those ailments by increased UCP1 in skeletal muscle. The “uncoupled mice” also had less body fat (or adiposity) and higher body temperatures and metabolic rates, among other biochemical changes.
I would rather have a version of UCP1 that I could switch between different levels of efficiency. Before going on a hike or after an accident or natural disaster it might make sense to shift UCP1 into a more efficient form. Basically, burn off excess energy when you can afford to do so but put your body into a high efficiency mode of operation when the need arises.
The development of drugs that reduce appetite should eventually reduce the benefit of turning UCP1 into a less efficient form. No need to burn off excess sugars and fats if you can make your brain not crave calories in the the first place.
Your genes seem like they are at war with each other. Very old ld people have genetic variations that protect them against other genetic variations they have.
August 24, 2007 – (BRONX, NY) – People who live to 100 or more are known to have just as many—and sometimes even more—harmful gene variants compared with younger people. Now, scientists at the Albert Einstein College of Medicine of Yeshiva University have discovered the secret behind this paradox: favorable “longevity” genes that protect very old people from the bad genes’ harmful effects. The novel method used by the researchers could lead to new drugs to protect against age-related diseases.
Next time someone marvels to you about the design of the human eye (which is really dumb if you look at the way nerves are routed to the light sensors called rods and cones) or other aspects of human anatomy keep in mind that you contain genetic variations that are bad for your health.
“We hypothesized that people living to 100 and beyond must be buffered by genes that interact with disease-causing genes to negate their effects,” says Dr. Aviv Bergman, a professor in the departments of pathology and neuroscience at Einstein and senior author of the study, which appears in the August 31 issue of PLoS Computational Biology.
A group of researchers are studying the genetics of some long-lived Ashkenazi Jews.
To test this hypothesis, Dr. Bergman and his colleagues examined individuals enrolled in Einstein’s Longevity Genes Project, initiated in 1998 to investigate longevity genes in a selected population: Ashkenazi (Eastern European) Jews. They are descended from a founder group of just 30,000 or so people. So they are relatively genetically homogenous, which simplifies the challenge of associating traits (in this case, age-related diseases and longevity) with the genes that determine them.
Participating in the study were 305 Ashkenazi Jews more than 95 years old and a control group of 408 unrelated Ashkenazi Jews. (Centenarians are so rare in human populations—only one in 10,000 people live to be 100—that “longevity” genes probably wouldn’t turn up in a typical control group. Longevity runs in families, so 430 children of centenarians were added to the control group to increase the number of favorable genes.)
The scale of their study was pretty limited. First, they only had 305 very old Ashkenazi Jews. Plus, they only looked at 66 genetic markers.
All participants were grouped into cohorts representing each decade of lifespan from the 50’s on up. Using DNA samples, the researchers determined the prevalence in each cohort of 66 genetic markers present in 36 genes associated with aging.
A far larger study with more centenarians and thousands of genetic markers tested would likely turn up many more genetic variations of interest. I repeat: We need a massive study of centenarian genetics that compares the entire genome of long lived and less long lived to find out which genetic variations boost life expectancy.
The researchers think they found a genetic variant of one gene, cholesteryl ester transfer protein (CETP), that protects against the genetic variant of another gene which codes for a lipoprotein, lipoprotein a (aka Lp(a)).
As expected, some disease-related gene variants were as prevalent or even more prevalent in the oldest cohorts of Ashkenazi Jews than in the younger ones. And as Dr. Bergman had predicted, genes associated with longevity also became more common in each succeeding cohort. “These results indicate that the frequency of deleterious genotypes may increase among people who live to extremely old ages because their protective genes allow these disease-related genes to accumulate,” says Dr. Bergman. The Einstein researchers were able to construct a network of gene interactions that contributes to the understanding of longevity. In particular, they found that the favorable variant of the gene CETP acts to buffer the harmful effects of the disease-causing gene Lp(a).
Elevated blood plasma Lp(a) is associated with increased risk of stroke and heart disease. That a CETP variant could reduce the risk posed by Lp(a) is not surprising. CETP variants appear to affect the size of LDL cholesterol particles and other research shows other influences that CETP has on apolipoprotein A1 concentrations.
We need much larger scale studies of centenarian gene expression and gene sequences to find genetic reasons why they live longer. We can use that knowledge to target genes for drug development. If genetic variations cause higher levels of expression of genes that turn out to allow us to live longer then we need to find out which genes those are and try to develop drugs that will turn up those genes. We also need drugs that will turn down the activity of genes that appear to accelerate aging.
The knowledge about which genes enable us to live longer only will allow us to slow the rate of aging. What we need even more are biotechnologies that let us reverse aging and rejuvenate the body. In particular, what I most want are stem cell therapies and tissue engineering technologies. Also, we need gene therapies and nanobots to use to repair the brain.
ST. PAUL, Minn -- A gene variation that helps people live into their 90s and beyond also protects their memories and ability to think and learn new information, according to a study published in the December 26, 2006, issue of Neurology, the scientific journal of the American Academy of Neurology.
The gene variant alters the cholesterol particles in the blood, making them bigger than normal. Researchers believe that smaller particles can more easily lodge themselves in blood vessel linings, leading to the fatty buildup that can cause heart attacks and strokes.
The study examined 158 people of Ashkenazi, or Eastern European, Jewish descent, who were 95 years old or older. Those who had the gene variant were twice as likely to have good brain function compared to those who did not have the gene variant. The researchers also validated these findings in a group of 124 Ashkenazi Jews who were between age 75 and 85 and found similar results.
"It's possible that this gene variant also protects against the development of Alzheimer's disease," said study author Nir Barzilai, MD, the director of the Institute for Aging Research at Albert Einstein College of Medicine in Bronx, NY.
Work is underway to develop a drug that emulates the effect of this life-extending version of the CETP gene. But I'd much rather get a gene therapy that'd enhance my liver cells to express the genetic variant for CETP that slows aging.
I've long thought the liver a key target for slowing whole body aging because it regulates blood lipid, lipoprotein, and cholesterol levels. This CETP gene variant (called CETP VV) is likely just one of many genetic variations waiting to be found that are expressed in the liver and can raise life expectancy. Another example genetic variation with life extending capabilities is Apolipoprotein A-I Milano high density lipoprotein (Apo A-I Milano HDL for short) clears out artery plaque and would also be a very beneficial gene with which to enhance one's liver.
Since livers age and become cancerous what we need are genetically engineered youthful replacement livers. The maximum benefit way to extend one's life through liver genetic engineering would be to grow a youthful replacement liver that has beneficial genes added. We can not do this yet. But in 10 or 20 years we should be able to take some existing liver cells, select out cells that have the least amount of accumulated DNA aging damage, do gene therapy on those cells in culture, then grow the cells up into a replacement liver. Next swap out your aged liver for a genetically enhanced younger liver. Your blood lipids will get changed by the new liver to slow the aging of your brain and body.
Led by Dr. Nir Barzilai, director of the Institute for Aging Research at Einstein, the researchers examined 158 people of Ashkenazi (Eastern European) Jewish descent who were 95 or older. Compared with elderly subjects lacking the gene variant, those who possessed it were twice as likely to have good brain function based on a standard test of cognitive function.
Later the researchers validated their findings independently in a younger group of 124 Ashkenazi Jews between the ages of 75 and 85 who were enrolled in the Einstein Aging Study led by Dr. Richard Lipton. Within this group, those who did not develop dementia at follow up were five times more likely to have the favorable genotype than those who developed dementia.
Dr. Barzilai and his colleagues had previously shown that this gene variant helps people live exceptionally long lives and apparently can be passed from one generation to the next. Known as CETP VV, the gene variant alters the Cholesterol Ester Protein. This protein affects the size of “good” HDL and “bad” LDL cholesterol, which are packaged into lipoprotein particles. Centenarians were three times likelier to possess CETP VV compared with a control group representative of the general population and also had significantly larger HDL and LDL lipoproteins than people in the control group.
People with the CETP VV variant had more HDL cholesterol and bigger particles in their blood.
The genetic variation causes people to produce less of a protein called cholesterol ester transfer protein (CETP). Barzilai says that CETP has two functions: it helps move cholesterol from the arteries to the liver, and it helps control the size of cholesterol particles circulating in the blood. People with the protective gene variant have higher levels of "good" HDL cholesterol and also produce bigger cholesterol particles, which scientists believe may not stick to blood-vessel walls as easily as small particles do.
CETP is on one of the 3 pathways that transfer cholesterol from HDL particles in the blood into the liver. So CETP is involved in regulating the amount of cholesterol in the blood.
Plasma high density lipoprotein (HDL) levels show an inverse relationship to atherogenesis, in part reflecting the role of HDL in mediating reverse cholesterol transport. The transfer of HDL cholesterol to the liver involves 3 catabolic pathways: the indirect, cholesteryl ester transfer protein (CETP)–mediated pathway, the selective uptake (scavenger receptor BI) pathway, and a particulate HDL uptake pathway. The functions of the lipid transfer proteins (CETP and phospholipid transfer protein) in HDL metabolism have been elucidated by genetic approaches in humans and mice. Human CETP deficiency is associated with increased HDL levels but appears to increase coronary artery disease risk.
Each tweak on genes causes many effects. CETP modification might or might not be the most effective way to improve blood lipids and slow brain and body aging. We might eventually find that CETP VV has side effects that are undesirable and that ApoA-I Milano will accomplish the same beneficial effects without some undesirable side effects. Or we might find CETP VV is better than ApoA-I Milano or some other genetic variants not yet discovered are better than either of them. Or maybe ApoA-I Milano and CETP VV work together synergistically to slow aging even more.
In three lines of transgenic mice the tissues expressing the human CETP mRNA were similar to those in humans (liver, spleen, small intestine, kidney, and adipose tissue); in two lines expression was more restricted. There was a marked (4-10-fold) induction of liver CETP mRNA in response to a high fat, high cholesterol diet. The increase in hepatic CETP mRNA was accompanied by a fivefold increase in transcription rate of the CETP transgene, and a 2.5-fold increase in plasma CETP mass and activity.
Brain rejuvenation is going to be the hardest rejuvenation task to accomplish. Anything that slows down brain aging is doubly beneficial. First off, your brain will function at a higher level longer during your working career and into retirement. That makes for better success at work and a happier life all around. Also, since the brain is going to be the hardest organ to rejuvenate we need to preserve it longer while we wait for effective brain rejuvenation biotechnologies.
More generally, while we desperately need therapies that do repair and replacement of aged parts we should not ignore the benefits and potential of slowing the aging process. Liver genetic engineering as an approach to slow the aging process is appealing because it looks much easier to do than full body gene therapy. If liver genetic engineering could buy us one or two decades of additional life that might be just the time we need to live long enough to still be alive when full body rejuvenation becomes possible.
Whether it is safe or harmful to pig out on large amounts of french fries cooked in corn oil may depend on which genetic variation of apolipoprotein A5 (APOA5) that you carry. People who carry the wrong APOA5 version and eat more than 6% of their calories from omega 6 fatty acids get high triglycerides and other bad blood lipid components.
Boston -- Researchers from the Jean Mayer USDA Human Nutrition Research Center (USDA HNRCA) at Tufts University and colleagues have found another link among genes, heart disease and diet. The study, published in Circulation, examined apolipoprotein A5 (APOA5), a gene that codes for a protein, which in turn plays a role in the metabolism of fats in the blood. The results show that people who carry a particular variant of APOA5 may have elevated risk factors that are associated with heart disease, but only if they also consumed high amounts of omega-6 fatty acids in their diets.
Corresponding author Chao-Qiang Lai, PhD, a USDA-Agricultural Research Service (ARS) scientist at the USDA HNRCA, and colleagues analyzed lipid levels and dietary assessment questionnaires of more than 2,000 participants in the Framingham Heart Study and quantified their intake of different types of fats.
Omega-6 fatty acids, as well as omega-3 fatty acids, are polyunsaturated fatty acids (PUFAs) and, according to a report from the National Institutes of Health Office of Dietary Supplements, most Americans consume about 10 times more omega-6s than omega-3s. Omega-3s are found in nuts, leafy green vegetables, fatty fish, and vegetable oils like canola and flaxseed, while omega-6s are found in grains, meats, vegetable oils like corn and soy, and also processed foods made with these oils. Both omega-3s and omega-6s, known as essential fatty acids, must be consumed in the diet because they are not made by the body.
"We know that some people are genetically predisposed to risk factors for heart disease, such as elevated low-density lipoprotein levels in the blood," says Lai, "and that APOA5 has an important role in lipoprotein metabolism. We wanted to determine if certain dietary factors change the role of APOA5 in metabolizing these lipoproteins and their components, such as triglycerides."
Lai and colleagues found that approximately 13 percent of both men and women in the study were carriers of the gene variant. Those individuals that consumed more than six percent of daily calories from omega-6 fatty acids displayed a blood lipid profile more prone to atherosclerosis (hardening of the arteries) and heart disease, including higher triglyceride levels.
The ability to get the DNA sequence of all your genome is starting to become useful. The information is starting to become practically useful for individuals and not just useful for scientists. DNA sequencing still costs orders of magnitude too much money. But the cost of getting a small subset of genes checked for problematic genetic sequences is much more affordable.
(Philadelphia, PA) - Building on previous work, researchers at the University of Pennsylvania School of Medicine have found that deleting an inflammation enzyme in a mouse model of heart disease slowed the development of atherosclerosis. What's more, the composition of the animals' blood vessels showed that the disease process had not only slowed, but also stabilized. This study points to the possibility of a new class of nonsteroidal anti-inflammatory drugs (NSAIDs) that steer clear of heart-disease risk and work to reduce it.
Drugs that block the same gene (or its protein product) that was knocked out in these mice might also stop the development of arterial plaque that clogs up our circulatory systems. Mouse knock-out experiments once again deliver the goods.
Senior author Garret FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at Penn, and colleagues report their findings this week in the online edition of the Proceedings of the National Academy of Sciences.
NSAIDs like ibuprofen (Advil) and naproxen (Naprosyn) relieve pain and inflammation by blocking the cyclooxygenases, or COX enzymes (COX-1 and COX-2). These enzymes help make fats called prostaglandins. COX-2 is the most important source of the two prostaglandins - PGE2 and prostacyclin - that mediate pain and inflammation. However, COX-2-derived PGE2 and prostacyclin may also protect the heart, and loss of this function - particularly suppression of prostacyclin - explains the risk of heart attacks from NSAIDs that inhibit COX-2, such as rofecoxib (Vioxx), valdecoxib (Bextra), and celecoxib (Celebrex).
The problems with COX-2 inhibitors have prompted the search for alternative drug targets that suppress pain and inflammation yet are safe for the cardiovascular system. One possibility is an enzyme called mPGES-1, which converts PGH2 (a chemical product of COX-2) into PGE2. Previous studies at other institutions in mice lacking mPGES-1 suggest that inhibitors of this enzyme might retain much of the effectiveness of NSAIDs in combating pain and inflammation. However, unlike COX-2 inhibition or deletion, the Penn researchers had found that mPGES-1 deletion did not elevate blood pressure or predispose the mice to thrombosis. This work began to raise the possibility that mPGES-1 inhibitors might even benefit the heart.
In the PNAS study, the researchers studied the impact of deleting the mPGES-1 gene in mice predisposed to hardening of the arteries. Removing the enzyme had a dramatic effect on the development of the disease. "Both male and female mice slowed their development of atherosclerosis," explains first author Miao Wang, PhD, a postdoctoral fellow in the Penn Institute.
The composition of the blood vessels of the transgenic mice suggested that the disease process had not only slowed, but also stabilized. Collaborators Ellen Pure and Alicia Zukas at the Wistar Institute examined the detailed structure of the diseased arteries. Deleting mPGES-1 resulted in a dramatic change in the cellular constituents of the atherosclerotic plaques seen in the transgenic mice. In the absence of the enzyme, the diseased vessels were depleted of immune cells called macrophages, which led to the predominance of vascular smooth muscle cells in blood vessel walls. In turn, this led to a switch in the form of collagen - a fibrous structure that contributes to the fabric of plaques - to a more stable and benign form.
"It seems that it is the complete reverse of the mechanism that creates problems for COX-2 inhibitors," says FitzGerald. Mice lacking mPGES-1 boost their production of prostacyclin, the major heart-protecting fat produced by COX-2. They do this by redirecting prostacylcin to vascular smooth muscle cells. The same mechanism explains the group's earlier findings on blood pressure and thrombosis.
"It remains to be determined whether specific inhibitors of mPGES-1 can replicate the consequences of removing the gene" explains FitzGerald, "And if so, whether these results will translate from mice to humans."
In the meantime, these results, say the investigators, will fuel interest in the possibility of a new class of "super NSAIDs," which may not just avoid the risk of heart disease, but also actually work to diminish it.
The build-up of artery plaque is going to become totally preventable and in short order. Diet alone already can reduce the risk enormously. Eat the ape diet if you want to lower your risk of heart disease, stroke and other diseases..
University of California, Davis researchers have shown that statins not only improve cholesterol levels, but also dramatically reduce disease-causing inflammation in patients with metabolic syndrome -- a condition defined by symptoms that include abdominal obesity and high blood pressure.
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The UC Davis team conducted a double-blind, randomized, placebo-controlled study in which they gave a standard daily dose of a statin (Simvastatin or placebo) to 50 patients with metabolic syndrome. After eight weeks, they measured cholesterol levels, as well as biomarkers of inflammation in the circulation, but more importantly, in cells pivotal in all stages of plaque formation, the monocytes. They found, as expected, that statin lowered low-density-lipoprotein- cholesterol and non-high-density-lipoprotein-cholesterol levels, both of which the American Heart Association guidelines target for treatment of metabolic syndrome.
Jialal and his colleagues also found marked reductions in two pivotal biomarkers of inflammation: C-reactive protein (CRP) and interleukin-6. While these markers are typically elevated in insulin resistance, a condition that precedes the development of diabetes, statin therapy reduced these levels by 36 percent and 44 percent, respectively.
Chronic inflammation is harmful and widespread.
As for people who have a need to take one of the existing NSAIDs, a recent pair of papers in the Journal of the American Medical Association found that Celebrex does not pose as large of a heart risk as Vioxx.
In one paper, three researchers at Harvard examined 114 clinical trials of Vioxx and other drugs and found that Vioxx was linked to substantially higher rates of increased blood pressure than was Celebrex, a similar painkiller, which is still sold.
In the other paper, two Australian researchers found that Vioxx appeared more dangerous than Celebrex or several older painkillers in observational studies, which examine the safety and effectiveness of drugs in real-world settings after they are approved.
David Graham of the FDA, writing as a private citizen, argues in JAMA that naproxen appears safest out of all the NSAIDs and probably is neutral in terms of risk of heart attack (MI or myocardial infarction).
The New York Times has an excellent article surveying what is known about the role genetic inheritence in determining life expectancy and mortality. Recent studies on twins point toward a much smaller than expected role for genetics in determing life expectancy.
His solution, a classic one in science, was to study twins. The idea was to compare identical twins, who share all their genes, with fraternal twins, who share some of them. To do this, Dr. Christensen and his colleagues took advantage of detailed registries that included all the twins in Denmark, Finland and Switzerland born from 1870 to 1910. That study followed the twins until 2004 to 2005, when nearly all had died.
Now, Dr. Christensen and his colleagues have analyzed the data. They restricted themselves to twins of the same sex, which obviated the problem that women tend to live longer than men. That left them with 10,251 pairs of same-sex twins, identical or fraternal. And that was enough for meaningful analyses even at the highest ages. “We were able to disentangle the genetic component,” Dr. Christensen said.
But the genetic influence was much smaller than most people, even most scientists, had assumed. The researchers reported their findings in a recent paper published in Human Genetics. Identical twins were slightly closer in age when they died than were fraternal twins.
But, Dr. Christensen said, even with identical twins, “the vast majority die years apart.”
On average identical twins die over 10 years apart. I would not have expected that result.
Even the role for genetic inheritance for cancer risk differences is seen as fairly small.
In a paper in The New England Journal of Medicine in 2000, Dr. Paul Lichtenstein of the Karolinska Institute in Stockholm and his colleagues analyzed cancer rates in 44,788 pairs of Nordic twins. They found that only a few cancers — breast, prostate and colorectal — had a noticeable genetic component. And it was not much. If one identical twin got one of those cancers, the chance that the other twin would get it was generally less than 15 percent, about five times the risk for the average person but not a very big risk over all.
Of course there are people who have genetic variations which put them at very high risk of cancer.
Alzheimer's risk has a larger genetic component.
Dr. Gatz and Dr. Pedersen analyzed data from a study of identical and fraternal Swedish twins 65 and older. If one of a pair of identical twins developed Alzheimer’s disease, the other had a 60 percent chance of getting it. If one of a pair of fraternal twins, who are related like other brothers and sisters, got Alzheimer’s, the other had a 30 percent chance of getting it.
But, Dr. Pedersen noted, Alzheimer’s is so common in the elderly that it occurs in 35 percent of people age 80 and older.
Note there are some complicating factors here. Most notably, some genetic variations put you at risk for some disease only if you do or do not do some certain thing. For example, a genetic variation for apolipoprotein E increases risk of Alzheimer's but if you have that apoliprotein E allele then diet can greatly reduce the risk. So if you live in a culture where the customary foods cancel out the genetic risk you aren't going to be at much greater risk from that genetic allele. But if you live in a culture where you eat customary foods which do not provide compensating protections then carrying that genetic allele will put you at much greater risk of Alzheimer's.
One theory of aging and longevity is that we randomly collect defects and damage during development and also during aging. Given that the process of collecting those defects is random their distribution is random. If you are lucky your defects will accumulate with a fairly even distribution throughout the body. That way it will take longer for one organ to collect enough defects to fail entirely. But if you are unlucky then by chance many of your defects will accumulate in one organ or one part of an organ (e.g. in a heart valve) or in one cell (e.g. a set of mutations that make the cell become cancerous) to the point of failure and then you'll die sooner. Twins won't live the same amount of time because they each will accumulate defects in a different random distribution.
So what's the take-away lesson from this article? There's no reason for complacency about your life expectancy. Say your parents or grandparents lived a long time. So what. That's no guarantee you won't get cancer tomorrow or have a heart attack next week. Your defects are accumulating randomly. You might be accumulating a cluster somewhere that is going to kill you years before other family members die. If you want to live a very long time then support SENS research. Anything short of SENS technologies can't save you from the damage building up within.
The whole article is worth reading.
Humans, mice, and flies show the same patterns of changes in gene regulation with age.
STANFORD — We can dye gray hair, lift sagging skin or boost lost hearing, but no visit to the day spa would be able to hide a newly discovered genetic marker for the toll that time takes on our cells. “We’ve found something that is at the core of aging,” said Stuart Kim, PhD, professor of developmental biology and of genetics at the Stanford University School of Medicine.
In a study published in the July 21 issue of Public Library of Science-Genetics, Kim and colleagues report finding a group of genes that are consistently less active in older animals across a variety of species. The activity of these genes proved to be a consistent indicator of how far a cell had progressed toward its eventual demise.
Until now, researchers have studied genes that underlie aging in a single animal, such as flies or mice, or in different human tissues. However, a protein associated with aging in one species may not be relevant to the aging function in a different animal. This limitation had made it difficult to study the universal processes involved in aging.
Kim’s work overturns a commonly held view that all animals, including humans, age like an abandoned home. Slowly but surely the windows break, the shingles fall off and floorboards rot, but there’s no master plan for the decay.
What we need to know: Which genes first start changing? Or which key regulatory switches start telling genes to start expressing differently? To put it more generally: What is the sequence of events that causes the genes to start behaving differently with age?
One possibility: The genes in the mitochondria (the sub-cellular organelles that generate energy molecules for the rest of the cell) could get mutated and damaged and then the genes in the nucleus start expressing differently due to signals coming out of the mitochondria.
Energy metablolism takes a big hit with age.
In the study, Kim and his colleagues looked at which genes were actively producing protein and at what level in flies and mice in a range of ages and in tissue taken from the muscle, brain and kidney of 81 people ranging in age from 20 to 80. The group used a microarray, which can detect the activity level of all genes in a cell or tissue. Genes that are more active are thought to be making more proteins.
One group of genes consistently made less protein as cells aged in all of the animals and tissues the group examined. These genes make up the cellular machinery called the electron transport chain, which generates energy in the cell’s mitochondria.
Kim said the gene activity is a better indicator of a cell’s relative maturity than a person’s birthday. One 41-year-old participant had gene activity similar to that of people 10 to 20 years older; muscle tissue from the participant also appeared similar to that of older people. Likewise, the sample from a 64-year-old participant, whose muscles looked like those of a person 30 years younger, also showed gene activity patterns similar to a younger person.
Biopsies of many organs in your body might tell you which organs are going to wear out first and which need replacements. With the sort of biotechnology we'll have 10 or 20 years from now we'll be able to start growing replacements for the worn out parts. Ideally, the replacements could be grown inside your own body and then connected up with surgery.
You can read the full article online: Transcriptional Profiling of Aging in Human Muscle Reveals a Common Aging Signature
We analyzed expression of 81 normal muscle samples from humans of varying ages, and have identified a molecular profile for aging consisting of 250 age-regulated genes. This molecular profile correlates not only with chronological age but also with a measure of physiological age. We compared the transcriptional profile of muscle aging to previous transcriptional profiles of aging in the kidney and the brain, and found a common signature for aging in these diverse human tissues. The common aging signature consists of six genetic pathways; four pathways increase expression with age (genes in the extracellular matrix, genes involved in cell growth, genes encoding factors involved in complement activation, and genes encoding components of the cytosolic ribosome), while two pathways decrease expression with age (genes involved in chloride transport and genes encoding subunits of the mitochondrial electron transport chain). We also compared transcriptional profiles of aging in humans to those of the mouse and fly, and found that the electron transport chain pathway decreases expression with age in all three organisms, suggesting that this may be a public marker for aging across species.
People who had worse muscle function also had gene expression patterns characteristic of more aged muscles.
The authors profiled gene expression changes in the muscles of 81 individuals with ages spanning eight decades. They found 250 genes and 3 genetic pathways that displayed altered levels of expression in the elderly. The transcriptional profile of age-regulated genes was able to discern elderly patients with severe muscle aging from those that retained high levels of muscle function; that is, the gene expression profiles reflected physiological as well as chronological age.
Another use for this information: Study people on different diets and lifestyles and see if particular diets or patterns of living cause particular organs to age more rapidly.
Some day I expect spouses to include DNA tests on body aging to argue that their spouses are aging them too rapidly.