Scientists at the Albert Einstein College of Medicine discovered that genes associated with aging also protect older people from effects of disease-causing gene variants. “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 Aviv Bergman, Ph.D., a professor in the departments of pathology and neuroscience at Einstein and senior author of the study.
To test this hypothesis, Dr. Bergman and his colleagues examined individuals enrolled in Einstein’s Longevity Genes Project. The program was initiated in 1998 and includes Ashkenazi Jews. They are descended from a founder group of about 30,000 people. Hence, they are relatively genetically homogenous.
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 that only one in 10,000 people live to be 100, thus the longevity genes probably wouldn’t turn up in a typical control group, the researchers s explain. Longevity runs in families, so 430 children of centenarians were added to the control arm to increase the number of favorable genes.
All participants were grouped into cohorts representing each decade of life span from the 50’s on up. Using DNA samples, the researchers determined the prevalence of 66 genetic markers present in 36 genes associated with aging in each cohort.
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. 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 report that they were able to construct a network of gene interactions that contributes to the understanding of longevity. In particular, they found that a favorable variant of the gene CETP acts to buffer the harmful effects of the disease-causing gene Lp(a).
From the 66 genetic markers examined in this study, the Einstein researchers are now going to assay one million genetic markers throughout the human genome. The goal is to find additional genetic networks that are involved in the process of aging.
The study will appear in the August 31 issue of PLoS Computational Biology.