Genetic predisposition to disease common in two supercentenarians

The study, published Jan. 3 in Frontiers in Genetics, reports a comprehensive analysis of the whole genome sequences of a man and a woman, both of whom lived past the age of 114. Supercentenarians (age 110+ years) are very rare, occurring at a rate of one person per five million in developed countries, and there is growing evidence supporting a strong genetic influence in survival to such ages.

The study shows that while the two supercentenarians carried as many disease-associated genes as the general population, their longevity suggests other protective mechanisms are at work.

The male subject had 37 genetic mutations associated with increased risk for colon cancer, indicating that he was in no way immune to that age-related disease. "In fact, he had presented with an obstructing colon cancer earlier in his life that had not metastasized and was cured with surgery. He was in phenomenal cognitive and physical shape near the time of his death," says Thomas Perls, MD, MPH, director of the New England Centenarian Study and senior author of the article.

The female supercentenarian also had numerous genetic variations associated with age-related diseases, including those related to increased risks for Alzheimer's, cancer and heart disease. She did have congestive heart failure and mild cognitive impairment, but these diseases did not become evident until after the age of 108 years.

"The presence of these disease-associated variants is consistent with our and other researchers' findings that centenarians carry as many disease-associated genes as the general population," Perls says. "The difference may be that the centenarians likely have longevity-associated variants that cancel out the disease genes. That effect may extend to the point that the diseases don't occur -- or, if they do, are much less pathogenic or markedly delayed toward the end of life, in these individuals who are practically living to the limit of the human lifespan."

"The study of these two supercentenarians is just the beginning, and genetic study of many more such subjects needs to be performed," adds Perls.

Data from the study will be available to researchers around the world at the National Institutes of Health (NIH) data repository.