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Born to age gracefully

Genes hold clues on who may live long and prosper

By Carolyn Y. Johnson
Globe Staff / July 2, 2010

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Five months shy of his 100th birthday, Louis Charpentier still rises every day at 9 a.m. to spend hours in his basement shop in suburban Leominster, carving delicate wooden figurines. Years after most people’s bodies and minds have failed, Charpentier climbs stairs with ease and recalls everything from the latest episode of “Dr. Phil’’ to the first train he ever saw, carrying soldiers who fought in World War I.

For years, scientists have been fascinated by biological outliers such as Charpentier as they seek to unlock the secrets of longevity.

Now, a team of scientists from Boston University has discovered a way to predict with 77 percent accuracy whether someone is likely to live to be exceptionally old.

Using cutting-edge genomics techniques on a group of 1,055 people born near the turn of the last century, researchers have identified a genetic signature of longevity. In work published online yesterday by the journal Science, they reported that 150 spots in the genome are associated with extremely long life.

“Exceptional longevity is not this vacuous entity that no one can figure out. I think we’ve made quite some inroads here in terms of demonstrating a pretty important genetic component to this wonderful trait,’’ said Dr. Thomas Perls, the senior author of the paper and the director of the New England Centenarian Study at Boston Medical Center.

The findings do not mean that healthy habits, such as exercise and diet, make no difference. Environmental and lifestyle factors are extremely important in determining lifespan, but when it comes to living to be exceptionally old — 10 to 30 years beyond the average person — genetic factors are thought to make an important contribution.

The research goal is to use the data to investigate what genes play a role in longevity, and to understand how it is that centenarians live so long and stay free of disease or disability. Researchers hope that lessons learned from extremely long-lived people could point to new ways to help everyone else age healthier.

Perls was quick to add that the study was intended to examine the genetic basis of healthy aging, and that it would be premature for people to take genetic tests to predict longevity.

Companies that offer consumers genetic tests — designed to tell people if they carry genetic variations that hold risk for diseases or traits ranging from Parkinson’s disease to lactose intolerance — have already drawn criticism from some scientists and doctors. The US Food and Drug Administration recently wrote letters to several companies that already offer such tests, requiring them to seek regulatory approval.

“You could conceivably produce a chip that would help predict people’s genetic predisposition to exceptional longevity. But I and all the authors of the paper want to instill a great deal of caution,’’ Perls said. “I start worrying a bit about what insurance companies and others might do with that information — I, for one, think it’s not ready from a social point of view.’’

In order to uncover genetic markers associated with extremely long life, researchers used statistical tools to analyze genetic samples from 801 people, aged 95 to 119. Led by Paola Sebastiani of the Boston University School of Public Health, the team looked at 300,000 spots in the genome of the centenarians and compared them with other people born later to find variations that were associated with longevity.

They found 150 areas in the genome that were associated with longevity, and then tested their tool on a separate group of 254 centenarians and 341 other people. They found that they could predict with 77 percent accuracy whether or not the people were exceptionally long-lived.

Researchers not involved in the study said the new work provides an interesting glimpse of exceptional longevity, but no obvious fountain of youth.

“I would say you could either see this as the glass being half-empty or half-full,’’ said Leonard Guarente, a biology professor at MIT who does aging research. The half-full scenario is there are now many new genetic spots to investigate that have something to do with exceptional longevity, he said. “The glass half-empty would say the analysis of these people is already bewilderingly complex and we’re never going to make any headway with this approach.’’

The results will have to be replicated in other groups of people to see if they hold up. The ideal analysis would have looked for genetic differences between people who lived to be 100, compared with people born at the same time, but such people have been dead for decades.

Dr. David Altshuler, a core member of the Broad Institute, a Cambridge genetics research center, said in an e-mail that the results were somewhat surprising, because when researchers have looked for the genetic underpinnings of common diseases, they do not usually find such a strong signal.

“I would have guessed that longevity would be even more complex,’’ Altshuler wrote.

It’s clear that lifestyle and environment play a large part in a person’s longevity. In studies of twins, researchers have found that just 20 to 30 percent of the variation in a person’s longevity is influenced by genes. But when it comes to extremely long life, genetics seems to play a critical role.

The spry, neatly dressed Charpentier doesn’t know how to explain his longevity. He doesn’t drink alcohol, he watches what he eats, and he quit smoking cigars 40 years ago. He wasn’t involved in the genetic study published yesterday, but — about to join the rare ranks of the one in 6,000 people who live to 100 — is one of the subjects being studied by scientists.

Not everything is perfect for Charpentier — he’s a little less steady on his feet than he used to be, and can’t lift weights like he did when he was young. But he still works in his shop, lives on his own, and remembers in detail the thoughts and experiences he had as a little boy.

“I feel I’m almost the same as when I was younger,’’ Charpentier said. “If it keeps on like I am now, I don’t mind if I live to be 110.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

Correction: An earlier version of this story misspelled the surname of Paola Sebastiani of the Boston University School of Public Health.

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