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Longevity Linked to Genes

Lifestyle remains an important factor


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Watch Paola Sebastiani and Thomas Perls discuss the study’s findings in a live chat about the Longevity Study on Wednesday, July 7, at 1 p.m. Video by Michelle Salzman

When it comes to living a long life, our fate is not entirely in our genes. But BU researchers believe that many of those who live a very long life (into their late 90s) have some genetic variances to thank for the extra years.

The scientists, lead by Paola Sebastiani at the School of Public Health and Thomas Perls at the School of Medicine, have found 150 genetic markers that predict with 77 percent accuracy whether people will live extremely long lives, which they defined as late 90s or older. In the United States, where the average life expectancy is 78, only one in 6,000 people make it to 100.

Despite the newfound genetic evidence, the researchers hastened to endorse exercise and a good diet as important extenders of life.

“Genetic data can indeed predict exceptional longevity without knowledge of any other risk factor,” the researchers wrote in the July issue of the journal Science. “This prediction is not perfect, however, and although it may improve with better knowledge of the variations in the human genome, its limitations confirm that environmental factors (e.g., lifestyle) also contribute in important ways to the ability of humans to survive to very old ages.”

The team studied more than 1,000 centenarians, comparing spots on their genomes with the genomes of a control group of almost 1,300 people. In addition to the 150 markers of extreme longevity, they found 19 “genetic signatures” that correlated with differences in the prevalence and age-of-onset of diseases such as dementia and hypertension. The researchers found that 45 percent of the oldest centenarians — those 110 years and older — had a genetic signature with the highest proportion of longevity-associated genetic variants.

“These genetic signatures are a new advance towards personalized genomics and predictive medicine, where this analytic method may prove to be generally useful in prevention and screening of numerous diseases, as well as the tailored uses of medications,” says Perls, founder and director of the New England Centenarian Study and a MED associate professor of medicine and geriatrics.

The researchers, who developed a novel statistical approach to analyze genotype data, believe that their methodology can be applied to other complex genetic traits, including Alzheimer’s disease, Parkinson’s, cardiovascular disease, and diabetes. Sebastiani, an SPH professor of biostatistics and the study’s lead author, says the new approach “reinvigorates the potential high utility of collecting and analyzing such data.”

Besides looking at which genetic variants were associated with longevity, the authors looked into the role of the absence of disease-associated variants. They did this by analyzing how many disease-associated variants each centenarian had, compared to each of the controls. Their analysis found little difference between the two groups, suggesting that the presence of genetic variants associated with longevity is more important than the absence of disease-associated variants.

The study was funded by grants from the National Institute on Aging (NIA) and the National Heart, Lung, and Blood Institute of the National Institutes of Health.

“This is a novel approach to studying genetic contributions to exceptional longevity,” says Winifred K. Rossi, deputy director of the NIA’s division of geriatrics and clinical gerontology. “It adds to a growing set of analytical tools that aim to identify and understand the complex genetic and environmental factors that lead to healthy, long life.”

In addition to Perls and Sebastiani, other authors include Nadia Solovieff and Stephen W. Hartley of the SPH biostatistics department; Daniel A. Dworkis, Efthymia Melista, and Monty Montano of MED’s department of medicine; Jemma B. Wilk and Richard H. Myers of MED’s department of neurology; Martin H. Steinberg and Clinton T. Baldwin of MED’s departments of medicine and pediatrics and Boston Medical Center; Stacy Anderson of MED’s department of medicine, section of geriatrics, and Boston Medical Center; and Annibale Puca of IRCCS Multimedica, Milano, Italy.

Read more about the longevity research of Thomas Perls and others in the Fall 2009 issue of Bostonia magazine.

Rich Barlow can be reached at barlowr@bu.edu.


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