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.
|Share |||Randall Parker, 2007 August 25 04:58 PM Aging Genetics|