Why Do Some People Live So Long?

One morning at the Hebrew Home for the Aged in New York, Nir Barzilai, M.D., administers a battery of tests to a vibrant 96-year-old woman named Etta Poley. There are blood tests and cognitive function tests. The doctor weighs Poley and asks about her family's medical history.

It turns out that Poley's mother died at 93; Poley's older brother lived into his 90s. As for Poley herself, a retired homemaker with two adult children, she's suffered only one serious illness—breast cancer, now in remission. At the Hebrew Home, Poley is known for her sharp mind and her mastery of television's Jeopardy!

"Because, Mrs. Poley, I'm trying to discover why you've outlived many of the doctors who long ago told you to quit smoking," Barzilai says, smiling.

Jokes aside, what Barzilai is probing for are clues to a very old question: Why do some people live exceptionally long lives? Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York, is gathering data for a study aimed at identifying genes that play a role in extreme longevity. If they can be located and their effects understood, then drugs could be developed to mimic the chemical signals that the genes send to the body.

"I'd say we're something like 10 years from that," says Barzilai, 50. "If things go right, it could happen in time to benefit baby boomers."

For eight years, geneticist Barzilai has been going around the country obtaining the family histories and blood samples of centenarians—people who have lived to be 100 years old, or close enough for his purposes. Additionally, his medical team collects information on the centenarians' children and, serving as the study's control group, the spouses of those children.

Around the globe—among the locations are Okinawa (Japan), France and American Amish communities—at least half a dozen other scientific groups are searching for longevity genes. DeCode, a private company with access to the genetic records of much of the population of Iceland, has found, among 90-year-olds, two genes protective of brain cells.

Barzilai's research subjects are Ashkenazim, a branch of the Jewish people that settled in Eastern Europe during medieval times. He's studying their American descendants because "you increase your odds of finding genes when you study a population that started out with a small group of 'founders,' was isolated for a long time and didn't marry outsiders often." All of this is true of 100-year-old Ashkenazim, though it's generally not true of their children and grandchildren. The centenarians' relatively small gene variability helped other scientists identify a gene linked to breast cancer.

A typical American has a life expectancy of about 78 years, with such potentially fatal diseases as cancer, diabetes and cardiovascular illness likely to appear during their 50s, 60s or 70s. Among the 370 centenarians Barzilai has studied, such diseases developed, if ever, much later, during their 80s, 90s or beyond.

Barzilai believes that centenarians have special genes protecting them from the diseases that kill most of the population at a much younger age. "If life is a minefield," he says, "the centenarians have some kind of genetic armament that gets them past the danger points."

But which genes do the job? A human being has an estimated 25,000 of them. Each gene has on it about 500,000 molecules that form DNA—microscopic bits of information regulating how specific proteins, cells and organs will function in an individual.

Back at his laboratory, an ultramodern warren of gleaming centrifuges, test tubes and laptops in the Bronx, Barzilai loads Etta Poley's blood sample into a machine that scans DNA. From that, a computer will create a kind of image, or profile, of her genetic makeup, or genome; each gene and each code on that gene has its own distinct markings and patterns. The computer will also run the information on Poley's genome against genetic data from all the other participants in the study—nearly 1,500 individuals. When it "hits" on similarities in the genetic patterns of the centenarians that are not shared by the control group—bingo!—that's a clue to a possible longevity gene.

"This work is a little like searching for a needle in a haystack," Barzilai says. "You've literally got billions of possibilities to find matches for. Thanks to all this newly invented computational equipment, we can now do it."

And he has. Since 2003 Barzilai has discovered three longevity genes, more than any other scientist. His discoveries appear to shield against heart disease, which is how they extend life span. Barzilai's team is also working on confirming the existence of a fourth longevity gene, originally identified by Thomas Perls, M.D., director of the New England Centenarian Study at Boston University School of Medicine. That gene, too, may play a role in heart disease prevention.

Barzilai loathes it when reporters describe him as a kind of scientific Ponce de Leon, questing for a fountain of youth. "No, no, no, we're not looking to help people live forever," he insists. "We're looking to enhance the quality of life of the elderly. Of course, in doing that, there's a good chance that there will be some life extension."

As the biographical side of the Einstein aging study progresses, researchers have uncovered similarities among the stories of the extremely long-lived. Contrary to the stereotyped old age of debilitation and chronic illness, many centenarians are astonishingly active and healthy, right until the very last moments of their lives. Their doctors say that they don't so much die as "give out."

It's that late-life heartiness that Barzilai hopes to understand better—and eventually bottle. That's good news for Etta Poley because she says having her genetic information and personal history be of use to others would make her proud. It's also great news to those of us who count on science to transform our own aging.

Do You Have What It Takes?