Diet Restriction: Eat Less, Live Longer?

A few years ago, Harvard researcher Dr. David Sinclair joined the growing ranks of scientists who believe that severely restricting calorie intake can slow down the aging process. Evidence for that surprising phenomenon emerged in the 1930s, when scientists learned that underfed rodents lived up to 40% longer than their well-fed counterparts. The results have since been duplicated in fruit flies, worms, monkeys and other lab animals. And preliminary research on humans suggests that some markers of aging--levels of blood glucose, blood pressure, cholesterol--improve on calorie-restriction (CR) diets.

So Sinclair put himself on the same sort of severe diet that members of the tiny but highly motivated Calorie Restriction Society follow. He lasted a week. "It was too tough," he says. "My hat's off to the calorie restricters. Now I'm hoping to find drugs that can give people the benefits of CR without the diet."

Those drugs haven't been perfected yet, but Sinclair and other researchers are making progress by trying to understand at the molecular level what it is about CR that seems to slow aging. Sinclair has found, for example, that resveratrol, a chemical found in red wine, increases life-spans of yeast and fruit flies. It works by amplifying the action of a molecule called SIRT1, which is present in all life forms and is produced in response to stress. "It's like a cell's 911 center," says Sinclair, and resveratrol is like a false alarm.

That fits with one of the leading theories about why CR works in the first place: starving the body puts it under mild, constant stress, priming it to resist the more severe stresses that make cells age--a sort of self-vaccination against decline. "With resveratrol," says Sinclair, "we're tricking the body into thinking it's not getting enough calories." If he can create a form of resveratrol that's easily absorbed by human cells and can demonstrate that it works without dangerous side effects, Sinclair may eventually come up with what amounts to an antiaging pill.

At the University of California, San Francisco, meanwhile, molecular geneticist Cynthia Kenyon is taking a different approach to aging research, identifying a number of genes in roundworms that help stave off disease and extend life. One such gene directs the action of a receptor for insulin and an insulin-like hormone called IGF1, and by manipulating it along with other genes, she can increase the worms' life-span sixfold. "It's not so much that they're just living longer," she says. "What's remarkable about these worms is how healthy they are."