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New study of centenarians links certain genetic variations to a long lifespan

By Rob Stein
Washington Post Staff Writer
Friday, July 2, 2010; A04

Scientists studying aging have long been fascinated by those rare individuals who somehow manage not only to live at least 100 years but also remain relatively healthy and spry even in their final years.

What's their secret? Is it clean living? A positive attitude? Or is it something in their genes?

A federally funded study released Thursday took an important step toward trying to answer that question by scanning the genes of a large number of centenarians and identifying genetic signatures that appear linked with living a long, healthy life.

"This is groundbreaking research," said Winifred K. Rossi, deputy director of the National Institute on Aging's Division of Geriatrics and Clinical Gerontology, which funded the research. "It's an important steppingstone towards helping us understand the complex genetic and environmental factors that lead to a healthy, long life."

Rossi and others cautioned that a healthful lifestyle and other environmental factors are significant in determining a person's lifespan, and that much more research is needed to explore the new findings. But the research indicates for the first time that there are specific genetic variations that can endow a person with an unusually long life.

"Exceptional longevity is not this vacuous entity that no one can figure out," said Thomas T. Perls of the Boston University School of Medicine, who led the study, published in the journal Science. "We've made quite some inroads here in terms of demonstrating a pretty important genetic component to this wonderful trait."

Perls and his colleagues analyzed the genes of participants in the New England Centenarian Study, which is the largest study of centenarians and their families in the world. The study involves about 1,600 centenarians and has been ongoing since 1995.

"A lot of people might ask, 'Well, who would want to live to 100?', because they think they have every age-related disease under the sun and are on death's doorstep," Perls said. "But this isn't true. We have noted in previous work that 90 percent of centenarians are disability-free at the average age of 93."

They also noticed that longevity seemed to run in centenarians' families, indicating that genetics must play a role.

So the researchers compared the genes of 1,055 centenarians with those of 1,267 other people to see whether they could identify unique patterns. Based on that work, the researchers identified 150 genetic variations apparently associated with longevity that could be used to predict with 77 percent accuracy whether someone would live to be at least 100.

"Seventy-seven percent is a very high accuracy for a genetic model, which means that the traits that we are looking at have a very strong genetic base," said Paola Sebastiani, a professor of biostatistics at the Boston University School of Public Health who helped conduct the study.

When researchers analyzed the genetic variations further, they identified 19 groups of variations that appear to correlate with different patterns of longevity. Some correlated with the longest survival; others correlated with those who lived the longest before developing diseases typical of the elderly, such as dementia.

The researchers also noted that the patterns did not include the absence of genes known to be associated with an increased risk for diseases common to aging, such as heart disease and Alzheimer's.

"This result, which is very surprising, suggests that what makes these people live a very long life is not a lack of genetic predisposition to diseases, but rather an enrichment of longevity-associated variance that may be protective," Sebastiani said.

The researchers also found that 40 percent of "super-centenarians," or those who live to be at least 110, had three genetic signatures in common.

The next step will be to try to reproduce the findings in other populations and identify the genes involved and what they do. Although the interaction of genetics, lifestyle and the environment is highly complex, the work could lead to treatments that might help extend life spans, the researchers said.

"I look at the complexity of this puzzle and feel very strongly that this will not lead to treatments that will get a lot of people to become centenarians, but rather to make a dent in the onset of age-related diseases like Alzheimer's," Perls said.

Researchers said it would be premature for a company to market a test for that purpose.

"What do you do when you're told you absolutely don't have this signature for exceptional longevity? Do you go and do a lot of risk-taking behaviors and say, 'Well, I'm hanging it up'? Or does it give you impetus to take all the more better care of yourself?" Perls asked. "I think a lot more study needs to be done."

The large number of genetic variations identified by the study presents a daunting challenge for researchers attempting to identify the specific genes and their function, several researchers said.

"The good news is you can identify genetic loci they think may be linked to longevity. The bad news is there are 150 of them that may contribute a tiny, tiny bit," said Leonard Guarente, who studies the genetics of aging at the Massachusetts Institute of Technology. "It's a question of whether the glass is half empty or half full."

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