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Life-span research points to genes

Study lists 150 markers common in centenarians

LOS ANGELES – They may not have discovered the fountain of youth, but scientists are beginning to unravel some of the mysteries of living past 100 – specifically, that it’s in your genes.

The study, led by Paola Sebastiani and Dr. Thomas Perls of Boston University and published Thursday online in the journal Science, analyzed the DNA of more than 1,000 centenarians – people over 100 years old – and found a set of small DNA variations called genetic markers that can be used to predict “exceptional longevity” with 77 percent accuracy.

But the story’s not a simple one: There’s no single “longevity gene.” For most of the golden agers, long life appeared to result from the cumulative effect of many of the 150 markers, and different markers showed up in different people.

“The study shows that there are different paths to becoming a centenarian,” said Boston University graduate student and co-author Nadia Solovieff. “People age in different ways.”

These markers may have some predictive power down the road for people who want to know if they’re destined for long life, researchers said. But genes alone are far from the whole story: For the vast majority of people, environment and lifestyle are also known to play important roles in aging. Only upon reaching these extremely old ages – which most people never see – do genes take center stage.

In the United States, where the average life expectancy is about 78 years, centenarians account for about one out of every 6,000 people. Supercentenarians, or people over the age of 110, are even rarer, at one out of 7 million.

“It’s kind of like winning the lottery,” Perls said.

Researchers said the task now is to characterize the genes and biochemical pathways identified in the study. Down the line, such information could potentially be used to develop drugs for age-related diseases such as heart disease, diabetes and Alzheimer’s disease, which occur at much lower rates in centenarians.

“This really opens the door to future research,” Perls said.

Though many potential genes were identified in the study, researchers were actually encouraged that the number wasn’t higher.

The genes may hold the secrets for treating or preventing many age-related diseases, since it appears that centenarians have something special that goes beyond simply dodging genes associated with individual diseases. A particularly surprising – and promising – finding from the study was that the centenarians had just as many markers that raise risk for age-related diseases as did a control group of almost 1,000 average-age people.

This suggests that genes associated with exceptional longevity somehow trump the negative effects normally caused by the disease genes, Perls and Sebastiani said.

The mechanism, however, is completely unknown.

The genes so far identified only explain a portion of the advanced age enjoyed by the study participants: Almost a quarter of the centenarians had very few of the markers identified in the study. The researchers plan to look at the DNA of these unusual subjects more closely to see if they can find additional longevity genes.

Though scientists are intrigued by these new genetic results, it has long been known that old age runs in families. Consider Jeanne Calment, the French woman who was born in 1875 and reached the age of 122 before she died in 1997 and has the longest confirmed human life span ever recorded.

Calment’s parents were also extremely long-lived. Her father died at 94 and her mother at 86, which would be considered healthy lives now but were remarkable for the time when they lived. Overall, 24 percent of her immediate relatives lived at least into their 80s, compared with 2 percent of the general population.

Calment, who met Vincent Van Gogh when she was 13, began fencing at the age of 85, gave up smoking when she was 120 and released a spoken-voice CD accompanied by rap and hip-hop two days before her 121st birthday.