Scientists Spot Gene Variants That Predict Longevity

THURSDAY July 1, 2010 -- Scientists have grouped together a series of genetic variants that can predict with 77 percent accuracy whether or not a person will live to 100 years of age.

Although experts and others probably could have predicted life span with even greater accuracy had they asked people how long their parents had lived, said Dr. Robert Marion, chief of genetics and development medicine and director of the Center for Congenital Disorders at Children's Hospital at Montefiore Medical Center in New York City, that method would not pave the way for advances in science, as this study likely does.

"Right now, this is kind of like a party trick but eventually, if you can identify early in life those individuals who have a predisposition to living longer and those who are destined to die young, you might actually be able to come up with some interventions for those who are going to die young and allow them to live longer," Marion said. "One of the big benefits of the new genomic medicine is that we're going to be able to do personalized medicine, and this is one way to approach that."

The study, funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute, appears in the July 2 issue of Science.

Right now, people in industrialized nations live an average of 80 to 85 years.

About one in 6,000 people in these parts of the world achieves centenarian status. Supercentenarians -- those who live to 110 or beyond -- occur at a rate of only about one in 7 million.

"We have about 80,000 centenarians alive at any time," said senior study author Dr. Thomas Perls. "The oldest person right now is about 116, in Japan." And the majority of people living to 100 and beyond are women.

"Centenarians are indeed a model of aging," said Perls, an associate professor of medicine at Boston University School of Medicine and Boston Medical Center. "A lot of people would not want to live to 100 because they think they would have every age-related disease under the sun and are on death's doorstep, but this isn't true. We have noted in previous work that 90 percent of centenarians are disability-free at an average age of 93. They compress their diseases towards the very end of their lives."

Given that long life spans tend to run in families, researchers have long suspected that genetics play a big role in this trait.

Here, the researchers conducted a genome-wide association study in 1,055 centenarians and 1,267 controls participating in the New England Centenarian Study, founded and directed by Perls.

From this, a genetic model that included 150 single nucleotide polymorphisms, or genetic variants, was able to predict with 77 percent accuracy how long a person was going to live.

"That's very high accuracy for a genetic model, which means that the traits that we're looking at have a very strong genetic basis," said study lead author Paola Sebastiani, a professor of biostatistics at Boston University School of Public Health.

The other 23 percent could be accounted for by environmental and lifestyle factors or genetic factors that simply are unknown at this point, Perls said.

The researchers also found 19 different genetic "signatures" in 90 percent of centenarians which correlated with "different patterns of exceptional longevity," said Sebastiani.

For example, some signatures correlated with the longest survival, and others with the most delayed onset of age-related illnesses, such as dementia or cardiovascular disease.

Surprisingly, said Sebastiani, "what seems to make people live very long lives is not a lack of genetic predisposition to diseases but an enrichment of longevity-associated variants that may counter the effects of disease-associated variants."

Basically, good genes seem to outweigh bad ones.

The long-livers did not seem to be clustered in any one region of the world.

No doubt, various companies will start marketing genetic tests claiming to predict how long one is going to live, but such tests are definitely not ready for prime time, Perls said.

"I think a lot of study needs to be done as to what guidance physicians and health-care providers can give to individuals as to what they do with this information," Perls said. In particular, there could be implications from an insurance point of view.

Twenty-three percent of people who didn't have one of these genetic signatures went on to live to 100, he pointed out, and having bad genes doesn't mean you don't have other good genes that would trump them.

The authors, who said they have no financial interests in the research, are setting up a web site where people who already know their genetic code can compute their longevity. It will be available through the New England Centenarian Study web site.

More information

The New England Centenarian Study has more on the secrets of long life.

Posted: July 2010


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