Genetic Signatures of Exceptional Longevity in Humans

Genes play a critical and complex role in facilitating exceptional longevity. The genetic influence becomes greater and greater with older and older ages, especially beyond 103 years of age.



Because many genes are involved, one needs to include many different genes at once (rather than one at a time) in what is called a genetic profile to accurately categorize who is a centenarian and who is not, based on genetic data alone.

We found 281 genetic markers that are 61% accurate in predicting who is 100 years old, 73% accurate in predicting who is 102 years old or older and 85% accurate in predicting who is 105 years old or older. In other words the prediction gets better with older and older ages beyond 100 which goes along with our hypothesis that the genetic component of exceptional longevity gets greater and greater with older and older age.

These 281 markers point to at least 130 genes, many of which have been shown to play roles in Alzheimer’s, diabetes, heart disease, cancers, high blood pressure, and basic biological mechanisms of aging.

Centenarians have just as many genetic variants that are associated with increased risk for age-related diseases (like Alzheimer’s, heart disease, stroke, diabetes and cancer) as people in the general population. Therefore, their tremendous survival advantage may in great part be due to the existence of longevity associated genetic variants that are protective and counter the negative effects of such disease gene variants.

People have genetic profiles that can be constructed from these 281 genetic markers (each of which has 3 variations) and these in turn are associated with specific probabilities of achieving very old age. Very interestingly, sub-groups of subjects have genetic profiles in common (what we call genetic signatures). Ninety percent of the 801 centenarians in the New England Centenarian Study could be grouped into one of 27 genetic signatures.

These genetic signatures are also associated with different predispositions to subgroups of centenarians such as those that completely escape heart disease, or those that delay Alzheimer’s disease until the last 5% of their very long lives. This method of generating signatures will be very useful for better understanding the underlying genetics of protection from age-related diseases, modulators of rates of aging and for the field of predictive and precision medicine.

Citation: Genetic Signatures of Exceptional Longevity in Humans. Paola Sebastiani, Nadia Solovieff, Andrew T. DeWan, Kyle M. Walsh, Annibale Puca, Stephen W. Hartley, Efthymia Melista, Stacy Andersen, Daniel A. Dworkis, Jemma B. Wilk, Richard H. Myers, Martin H. Steinberg, Monty Montano, Clinton T. Baldwin, Josephine Hoh, Thomas T. Perls. PloS ONE 2012. DOI: 10.1371/journal.pone.0029848.

Many of the above genetic findings were replicated in a combination of 5 collaborating centenarian studies.