The Century Club

Researchers scour centenarian genomes for clues to long life.

Only a hardy few of Duke Magazine’s readers were around when the university hired its first campus barber or published its first yearbook. If you’re one of them, David Goldstein wants to talk to you.

Goldstein, a professor of molecular genetics and biology, isn’t interested in haircuts or yearbooks per se, but rather in the vitality of people who have survived as long as those campus traditions. As part of a national study, he and the Duke Center for Human Genome Variation are collecting DNA from volunteers who have lived 100 years or more in hopes of identifying genes that correlate with longevity.

Such genome-wide studies have become more common as the technology to analyze whole genomes has improved. Researchers can now scour genetic data from thousands of people to find genes associated with common health problems. In the case of the centenarian study, scientists hope analyzing the genomes of people who have survived for more than a century will reveal genes that protect them from the harmful effects of aging.

The Duke team, however, is exploring a different possibility. “Our hypothesis is that centenarians live a long time because their genomes don’t have as many harmful mutations,” says Goldstein.

Our genes carry thousands of tiny mistakes—copying errors— that pile up over generations. Some mutations are known to cause specific problems, such as genetic variants that increase the likelihood of certain cancers, while others have no effect on health. Goldstein and his team think the key to longevity may be having a relatively mistake-free genome—in other words, one that minimizes the potentially deleterious effects of too many mutations.

“Other researchers are looking for protective variants, but we’re looking for a relative absence of things,” says Liz Cirulli Ph.D. ’10, a postdoctoral fellow working on the study.

The centenarian study is only one year in, and Goldstein and Cirulli have no idea how long it will take to see if their hypothesis is right. “It might be years, or we might have statistical signifi- cance in our next sample,” says Goldstein. One challenge will be finding enough centenarians to participate, since the overall population of people above 100 is small to begin with.

But even with enough data, finding genetic associations is not as simple as matching letters of code. “It’s common to think that genetic effects are simple, but in reality, they interact with one another in countless ways,” Goldstein says. “When it comes to understanding genetics, we are almost nowhere. We are at the absolute beginning.”

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