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The Nation

Aging Targeted With Science, Not Snake Oil

August 03, 2003|Jeff Donn | Associated Press Writer

BOSTON — A young man climbs from bed, stares into a mirror and glimpses his future.

He has just turned 34. His body is trim, his hair thick and dark. But what's that around his eyes? Those crow's-feet are getting harder to ignore. And do his teeth look a bit ground down by decades of chewing, or is it his imagination?

He will probably repeat the drill tomorrow, and the next day and the next -- about 16,000 more times if he, like the average American, dies at 80. "I don't think 80 years is long enough. There's a lot of things I want to do," he laments.

But what can he -- or anyone -- do about getting old? He can't stop it, any more than he can dispel rain clouds roiling on the horizon, any more than ancient alchemists could distill a real elixir of immortality.

Or can he?

His name is David Sinclair. A biologist at Harvard Medical School, his job is to prevent aging.

Catapulted by advances in biotechnology, scores of researchers have begun to pinpoint genes that may prolong human life while delaying its late-stage diseases, frailties and maybe even gray hair and wrinkles.

Their remarkable successes in laboratory animals -- such as worms that live four times longer than normal -- have already germinated several drug companies. They hope to develop compounds to stretch healthy lifetimes beyond limits once presumed to be fixed.

Some respected researchers envision millions living as long as Jeanne Calment of France, who died at age 122 in 1997. Tom Johnson, a University of Colorado geneticist, believes people could one day live to be 350, spanning the ages like Methuselah and other biblical patriarchs.

"I am absolutely convinced we are going to be able to extend human life," Johnson says. "This is not science fiction."

Under the best circumstances, a life-prolonging drug could conceivably arise in five years, says longevity guru Cynthia Kenyon, a molecular geneticist at UC San Francisco.

Although enthusiastic, others predict only modest advances in the near future because aging is such a fundamental and complex process. "I think it would be sensationalist and crazy to think we'd be seeing people living to 120, 130," says Thomas Perls, a Boston University aging specialist who studies the genetics of centenarians.

Although no one knows what can be accomplished or how soon, an intense methodical quest is under way to turn off aging with science instead of snake oil. *

Whatever else they accomplish, the hyperdriven, often brash scientists in this new field of aging genetics are already challenging the classic theories of aging and disease.

For centuries, aging has been understood as a scattered, chaotic, inevitable breakdown of the body and its organs. Like a car with too many miles, it eventually wears out. You can keep fixing parts, but others soon break down.

There was special reason for doubt in the genetic approach to slowing aging. Evolutionary theory dictates that we inherited genes that most helped our ancestors reach sexual maturity, not ones that helped or hurt them afterward.

If so, a genetic trigger for aging would be a long shot, if not for one event.

At first, it was more of a biological curiosity. In the 1930s, Cornell University nutritionist Clive McCay discovered that underfed rats live a lot longer than others. Just cut calories by about 30%, balance their diet, and they survive about 40% longer or more. The technique works in fish, fleas and other species. Early data suggest it works in monkeys too, say researchers at the University of Wisconsin and the National Institute of Aging.

Underfeeding has revealed a second remarkable power: It keeps animals healthy, largely free of aging ailments like cancer and heart disease. They stay strong and energetic. They even keep more fur.

"On one side, the calorie-restricted mice are jumping, and running around, and looking young," says Stephen Spindler, a biochemist who does such experiments at UC Riverside. "On the other side, the litter mates look old. They're gray, and they have more balding. They move less. It makes me want to go on a diet."

Even if it proved to work in people -- still an open question -- few would likely tolerate such a Spartan diet.

Maybe dieting isn't necessary, though. Researchers suspected that the effects of underfeeding point to some built-in biological switch after all: a set of master genes that can delay aging. Could they be found? And could their effect be mimicked by a drug that boosts or blocks the right proteins, the soldier molecules that do the work assigned by genes?

Kenyon, of UC San Francisco, knew of a microscopic roundworm that, when starved or overcrowded, slips into suspended animation. In this hardened condition known as dauer, it can hold out for months. It would otherwise die within about three weeks.

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