Never Say Die

By the time it reaches the age of 18 days, the average roundworm is old, flabby, sluggish and wrinkled. By 20 days, the creature will likely be dead—unless, that is, it's one of Cynthia Kenyon's worms. Kenyon, director of the Hillblom Center for the Biology of Aging at the University of California, San Francisco, has tinkered with two genes that turn simple worms into mini-Methuselahs, with life spans of up to 144 days. "You can beat them up in ways that would kill a normal worm—exposing them to high heat, radiation and infectious microbes—and still they don't die," she says. "Instead, they're moving and looking like young worms. It's like a miracle—except it's science."

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Since the days of Ponce de León, if not before, people have been seeking the elusive Fountain of Youth. Until recently, such pursuits were the realm of quacks and charlatans. And there are still plenty of snake-oil salesmen out there on the Internet and in so-called anti-aging clinics, hawking everything from longevity-bestowing Ecuadoran waters (which are probably harmless) to growth hormones (which could be downright dangerous for adults). But serious scientists are now bringing respectability to the field, unraveling the secrets of aging on a cellular level and looking for ways to slow it down. And while the science is still young (so to speak), legitimate longevity-boosting treatments could be available in 10 to 15 years—although the gains would be more modest than in Kenyon's worms.

The pursuit is not as quixotic as it may seem. Some critics of the scientific quest for longevity say it's God's will that we should die when our time comes. But in the past century, a clean water supply, antibiotics, vaccines and improved medical care have boosted life expectancy at birth by roughly 50 percent in the United States—from 48 for men and 51 for women in 1900 to 75 for men and 80 for women today. No one seems to object to that. "I'm 54," says Felipe Sierra, director of the division of aging biology at the National Institute on Aging. "A hundred years ago, I would have been dead by this age." Others argue that keeping people alive longer will further strain the social safety net. Yet for most scientists, the goal is not to tack years of sickness onto the end of life. "The goal is to extend youth," says Harvard molecular biochemist David Sinclair, who is working with a potential anti-aging compound called resveratrol. "I want to keep people healthier for longer and lessen the burden on the economy."

Studies are already yielding important clues on what produces healthy aging. One obvious answer is a healthy lifestyle, with plenty of exercise and a diet that includes lots of fruits, vegetables and whole grains. Seventh-day Adventists eat a vegetarian diet, don't smoke and spend a lot of time with family and church groups, which helps reduce stress. "They routinely live to 88 or so, which suggests those are ages most of us could attain with a healthy lifestyle," says Dr. Thomas Perls, director of the New England Centenarian Study.

But to make it to 100, like the 1,500 participants in Perls's study—or 110, like his "supercententarians"—it takes more than virtuous behavior and avoiding a collision with a Mack truck. A person needs genes that slow aging and boost defenses against age-related diseases. About half a dozen such genes have been identified out of perhaps 100 or so that might exist. The exceptional people with these genes seem to spend very little time sick—even when they defy all the rules. "We had one man who smoked three packs of cigarettes a day," says Perls. "He gave up smoking at 90, but he still drank three martinis a day—and he was out repairing his roof the day before I visited him. He died at 103."

Some of these beneficial genes appear to be involved in metabolic pathways related to growth, as well as the processing of fat and cholesterol. Kenyon manipulates a gene in her worms that reduces the action of insulin and a related hormone called IGF-1. "Lowering these hormones activates a gene called Foxo," she says, "which stimulates a whole host of responses that protect cells—boosting the immune system, increasing antioxidants, keeping proteins folded correctly." A study of Ashkenazi Jewish centenarians this year also found variations in genes governing IGF-1. A second study found protective changes in the Foxo genes of healthy 95-year-old men.