Aging Switch a Target for Longevity Drugs
Enzyme activated by touted life extender resveratrol, found in red wine

By Gabe Romain

Credit: Robert Blasche
Drink to your health: The discovery of a molecular link between eating and aging supports theories about the life-extending benefits of resveratrol, found in red wine

The key to a long, lean, healthy life may lie in a molecular switch that controls whether a mammal stores or sheds fat—and the switch is activated by a substance in red wine.

Researchers at the Massachusetts Institute of Technology in Cambridge have found a molecular link between eating and aging that could lead to the development of drugs that allow humans to reap the benefits of caloric restriction without dieting.

The discovery also lends support to theories about the life-extending capabilities of resveratrol, a substance in red wine that animal studies suggest can increase healthy lifespan.

"For the first time, this study gives us a glimpse of how calorie restriction works at the molecular level," says MIT researcher Leonard Guarente. "And it will ultimately lead to health benefits in people."

Buying time

Researchers have known for some time that caloric restriction can extend lifespan in a wide spectrum of organisms, including, mice, rats, yeast and worms.

Caloric restriction has also proven to delay the onset or reduce the incidence of many age-related diseases such as cancer and diabetes.

It has been hypothesized that caloric restriction works by activating a family of enzymes called sirtuins.

Researchers think that sirtuins are activated as a response to stressful conditions and cue organisms to switch on a survival program.

Fat burner

Guarente—who has made a career out of studying sirtuins—and colleagues have now found that a sirtuin called Sirt1 promotes fat metabolism in mice.

Mammals store fat in special cells called white adipose tissue. When caloric intake is reduced, this tissue stops storing fat and begins to release it.

Fat is metabolized by the body when the Sirt1 protein senses short-term famine and turns off mechanisms that normally keep fat stored in fat cells.

Because white adipose tissue also makes hormones such as leptin, which inhibits an appetite stimulant produced by the body, Guarente speculates that by putting hormones into the bloodstream, fat cells also tell the body how fast to age.

"Conversely, fewer fat cells tell the body that it's time to hunker down for survival," says Guarente. "This means that evolutionarily speaking, fat plays a very important role."

Molecular trickery

Although fat or lack of it has vast implications in the lives of people, strict diets are difficult to maintain for extended periods.

Mimicking the molecular effect of caloric restriction without actually dieting would therefore be of great benefit.

"If we could make a drug that would bind to Sirt1 and fool the body into thinking that it needed to release that fat, then maybe people could get the benefits of calorie restriction without the side effects," says Guarente.

Interestingly, resveratrol—a compound cited in explaining the French paradox, which describes how high-fat eating French people might live long by drinking red wine—has been found to activate Sirt1.

The next step for his line of research, says Guarente, is to determine if an increase in Sirt1 in the body leads to a higher rate of metabolism.

This could help bring together several pieces of the longevity puzzle, as researchers recently discovered that mice with a high metabolism live longer than their low metabolism counterparts.

The Sirt1 study is published in the journal Nature (read abstract).

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