Resveratrol: Live Long Eating More

David Sinclair and his collaborators think not only that the protective effects of fasting occur in people, but that they can be supplied in a pill. Research by Sinclair and his colleagues pointed to an ingredient in red wine called resveratrol as a candidate for triggering the life-lengthening benefits of dieting in humans. Their research was published August 24, 2003 in the online version of the journal Nature.

Curiously, the scientists may have found the answer to a famous paradox about the French. The paradox goes like this: even though the French consume very fatty food considered risky for the heart, they live as long as everyone else. The French also drink a lot of red wine, which has long been suspected as the reason for their longevity.

So far, resveratrol has only been a fountain of youth for laboratory yeast and fruit flies.

The laboratory yeast now benefiting from resveratrol helped lead to the chemical's discovery in the first place. Leonard Guarente began looking for long-lived yeast in his Massachusetts Institute of Technology laboratory in the early 1990s. In 1997, he and Sinclair found a strain of yeast that could outlast the others-and this strain had an active sir2 gene. Guarente later found that normal yeast that don't belong to this long-lived strain will activate sir2 if they are starving.

Sinclair and Konrad Howitz, a colleague at Biomol Research Laboratories in Plymouth Meeting, Pennsylvania, screened a large number of chemicals hoping to identify a few that would enhance the activity of sirtuin, the enzyme made by sir2. Such a chemical could be used in place of fasting to take advantage of sir2's beneficial effects. Using a test they designed to measure sirtuin's activity, they identified two chemicals, both members of the family called polyphenols. After screening a batch of polyphenols, they found a chemical that stimulated sirtuin more than any of the others: resveratrol.

Concerning his possible solution of the French paradox, Sinclair told the New York Times he was amazed that "in an unbiased screen we pulled out something already associated with health benefits."

Guarente estimates that, assuming the life-lengthening effects of fasting or resveratrol are the same in humans as in laboratory organisms, people taking a drug that contains resveratrol might extend their normal life expectancy by one-third. For example, a person aged 50 years and expected to live to 80 might instead live to 90.

Other experts are less optimistic about the life-extending capacity of fasting and resveratrol. "At this point we have no indication that there will be a benefit in people," David Finkelstein, project officer at the National Institute of Aging, told the New York Times.

As for red wine itself, Toren Finkel, head of cardiovascular research at the National Heart, Lung and Blood Institute, told the New York Times, "I would be cautious in sending out the message that one glass of wine a day will make you live 10 years longer. The concentration of resveratrol in different wine differs." The newspaper reported that levels of the chemical are higher in red wines made from grapes grown under stressful conditions, such as a cool climate or the presence of a fungal infection.

Biologists believe resveratrol may unlock an ancient mechanism, whose purpose may be to protect an organism when food is scarce, preserving the organism for reproduction in better times.

Sources

"It's Never Too Late." James W. Vaupel, James R. Carey, and Kaare Christensen. Science, September 19, 2003, page 1679.

"Study Spurs Hope of Finding Way to Increase Human Life." Nicholas Wade. The New York Times. August 25, 2003, page A10.

"Forget Botox. Anti-Aging Pills May Be Next." Andrew Pollack. The New York Times. September 21, 2003, section 3, page 1.

"Demography of Dietary Restriction and Death in Drosophila." William Mair, Patrick Goymer, Scott D. Pletcher, and Linda Partridge. Science, September 19, page 1731.

"Small Molecule Activators of Sirtuins Extend Saccharomyces Cerevisiae Lifespan." Konrad T. Howitz, Kevin J. Bitterman, Haim Y. Cohen, Dudley W. Lamming, et al. Nature, September 11, 2003, page 191.