“Longevity Genes” Solve Centenarian Paradox

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August 28, 2007

“Longevity Genes” Solve Centenarian Paradox

Ancient_bristlecone Scientists have long been baffled as to why some people live so much longer than others. Diet and exercise account for some of it, but researchers have found that genetics also factor heavily into the equation, and that long life is somewhat hereditary as it is with the ancient bristlecone pine shown left that was alive when Caesar ruled Rome.

However, centenarians are known to have just as many—and sometimes even more—harmful gene variants compared with those who die much younger. So what is the secret advantage? That’s a question the experts have been eager to find an answer to.

Scientists at the Albert Einstein College of Medicine of Yeshiva University have finally unlocked the secret behind the paradox. They were able to identify specific favorable “longevity genes” that offer protection from the harmful effects of “bad genes”. The discovery could lead to new drugs that protect against age related diseases.

“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.

To test the 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 homogeneous, which makes it easier to associate 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 any human population—only one in 10,000 people live to be 100—that “longevity” genes probably wouldn’t turn up in a typical control group.)

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.

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).

If future research confirms that a single longevity gene can buffers against multiple disease-causing genes, then drugs that mimic the action of the gene could protect against a variety of cardiovascular disease and other age-related ailments.

Posted by Rebecca Sato

Related Galaxy posts:

The Story of a Biologist & the Extension of the Human Life Span

Stress Causes Cancer -New Research Finds

Pathway to Longevity Discovered

Links:

http://www.aecom.yu.edu/home/news/PRdetails.asp?isPR=1&id=372

http://vinnysa1store.blogspot.com/2007/08/einstein-researchers-use-novel-approach.html

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