Want to live 350 years? Experts say it's doable.

By JEFF DONN, Associated Press

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 same check tomorrow, and tomorrow, and tomorrow -- about 16,000 more times if he, like the average American, dies at around 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. He is 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 successes in laboratory animals -- like 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, thinks people could one day live to be 350 years old, 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 the University of California-San Francisco.

Whatever else they accomplish, the 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, except for one thing.

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 percent, balance their diet, and they survive about 40 percent longer or more.

The technique works in fish, fleas, and other species, and 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 the University of California-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 the University of California-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.

This state is directed by a gene, daf-2, that controls growth by helping manufacture an insulin-like hormone. Kenyon wondered if worms with disabled variants of this gene might turn into spry, wiggly Methuselahs. In her tests, they did. Similar manipulations worked in flies and mice. A raft of such discoveries in the 1990s helped legitimize the new field of aging genetics.

Over the past 15 years, researchers have discovered several dozen genes that prolong life significantly in yeast, roundworms, fruit flies and mice. As in underfed animals, they appear to put off not just death, but the hobbling conditions of old age.

Most of these genes carry deadpan scientific monikers: p66shc, ctl-1, Lamin A. Others were mercifully christened in whimsy like age-1, clock, Methuselah, and INDY -- for "I'm Not Dead Yet," a name inspired by a line from a Monty Python movie.

Many longevity genes first tracked in animals have human counterparts. Other genes were first spotted in humans.

Nerve researcher Gabrielle Boulianne, of the University of Toronto, was studying one of them in 1998. She was researching amyotrophic lateral sclerosis, the degenerative nerve condition known as Lou Gehrig's disease.

It had been linked to a gene known as SOD1, which treats metabolic waste products. Since fruit flies carry a twin gene, she transplanted and supercharged the human gene in their nerve cells, hoping to develop a research model for the disease.

What happened next was unforeseen: The flies lived an average of up to 40 percent longer. "In some respects, I was shocked," Boulianne says. "That was not the original goal."

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