Longevity? It's in the Genes for Centenarians

Those who live to 100 or longer may have their genes to thank, researchers say.

July 1, 2010— -- The key to exceptional longevity -- living to 100 or more -- may be in your DNA, researchers said.

A study of almost 1,000 people aged 100 or older has revealed 150 genetic variants that set centenarians apart from other people about three-quarters of the time, according to Dr. Thomas Perls of Boston University and colleagues.

In their report, published online in the journal Science, Perls and colleagues identified 19 clusters of genetic variants associated with exceptionally long life that correlated with the risk of developing age-related conditions such as dementia and high blood pressure.

The researchers noted that the average human lifespan in developed countries now ranges from 80 to 85 years.

"Environmental factors (lifestyle choices relating to diet, exercise, smoking habits, etc.) as well as genetic factors are believed to contribute to healthy aging," they wrote. "The results of human twin studies suggest that only 20-30 percent of the variation in survival to an age of about 85 years is determined by genetics."

So although environmental factors are involved, "genetics is playing a very important role in the wonderful trait," Perls told reporters in a telephone press conference.

Perls cautioned that the current study is not likely to lead to an "elixir" that could allow people to live to be 100 or more, largely because of the complex interactions among dozens of genetic variants that he and his colleagues found.

"This will not lead to treatments that will get a lot of people to become centenarians," he said, "but rather [will] make a dent in the onset of age-related diseases," although even that will require much more study.

Indeed, he said, the key to an extremely long life appears to be a capacity to delay the onset of age-related disability and diseases, such as cardiovascular disease, including stroke, and dementia.

"Centenarians are a model of healthy aging, as the onset of disability in these individuals is generally delayed until they are well into their mid-nineties," Perls and colleagues wrote.

Genes May Protect Some From Age-Related Disease

In previous work, Perls and colleagues showed that 90 percent of centenarians live disability-free until age 93 on average. The few people who lived to be 110 or older, Perls added, were able to "compress both disability and disease even further" into the last years of their lives.

The current genome-wide association study gives some clues as to how these individuals might have been able to achieve that, according to lead author Paola Sebastiani, also of Boston University.

One possible explanation, she said, might be that centenarians had fewer genetic variants that predispose people to age-related illnesses. But a comparison of the prevalence of such "disease-associated variants" did not differ substantially between centenarians and controls, she said.

That suggests that the genetic variants associated with long life involve ways of overcoming the effects of disease-associated gene variants, she said.

About 15 percent of the controls also appear to have a "predisposition to exceptional longevity" based on the genetic model -- a proportion considerably higher than one centenarian in 6,000 observed in the general population.

That could be because the controls in this analysis are not a representative sample of the general population, Sebastiani said.

On the other hand, the researchers noted in their report, the finding is "consistent with the suggestion that many more people than previously suspected have the potential, at least genetically, to survive to an exceptional age."

Interestingly, one cluster that included 30 centenarians had almost no longevity-associated variants, the researchers found. It's possible that's just good luck or healthy behavior, Perls and colleagues said, but it may also be true that rare genetic variants -- not analyzed in the study -- can take the credit.

That idea is bolstered by family histories, they said. Data was available for 17 of the members of the cluster, of whom 59 percent had a strong family history of longevity.

Centenarians Deserve Closer Look, Researchers Say

A closer look at the genes of those volunteers, said Perls and colleagues, "may be particularly fruitful."

The study is "very exciting for the whole field of genetics and genomics and personalized health care," said Dr. Kathryn Teng of the Cleveland Clinic, who was not involved in the study but who is director of clinical integration of personalized health care at the hospital.

"It can potentially give us a lot of information -- now, but also in the future -- to target wellness, and risk for disease and also to develop potential medications or treatments," she told MedPage Today in an interview at which a public information officer was present.

But, Teng cautioned, the data from the study is not ready for application in the clinic.

"From a clinical practice standpoint, when I'm seeing patients, this is really not useful and helpful right now," she said. Instead, doctors will likely have to continue doing what they have been doing -- counseling their patients on how to lead healthy lives.

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