Healthier Aging

July 8, 2008 — -- Aging mice fed a chemical found in red wine were healthier in their twilight years, scientists have confirmed, although the rodents didn't necessarily live longer.

The anti-aging effects of the compound, resveratrol, mimic those of a calorie-restricted diet, which has been shown to give mice, dogs, and worms longer, healthier lives. Although resveratrol only extended the lives of obese mice in this latest study, it made all the animals healthier. They were spared the worst of some of the declines that come with old age, and they had healthier cardiovascular systems and stronger bones than did untreated animals. Non-obese mice fed resveratrol also had significantly lower total cholesterol. The study was done by the National Institute on Aging, as a follow-up to 2006 findings that resveratrol improves the health and longevity of overweight, aged mice.

The study offers yet more evidence of the possible anti-aging benefits of resveratrol. "Is this too good to be true?" asks Harvard Medical School's David Sinclair, one of the authors of the paper, which appears this week in Cell Metabolism. "I think we'll know in the next few years." Sinclair initially showed the anti-aging effect of resveratrol several years ago. Sirtris Pharmaceuticals, the company that he cofounded to develop anti-aging drugs, including ones based on resveratrol, was recently sold to GlaxoSmithKline for about $720 million.

Sinclair and his colleagues gave one-year-old mice--that's middle-aged, in mouse years-- high doses of resveratrol. It's found in the skins of grapes--which are left on the fruit when red wine is fermented but removed from white wine before fermentation--and in lower amounts in peanuts and some berries, including cranberries and blueberries.

Resveratrol had a broad range of health benefits for mice, the researchers confirmed. The mice had fewer cataracts, better bone density, healthier cardiovascular systems, and better motor coordination than did untreated animals, and resveratrol also made obese mice more sensitive to insulin.

"Let's hope it will do the same things for humans," says Mark Leid, a professor in the Department of Pharmaceutical Sciences at Oregon State University. He wasn't involved in this work.

Other studies have found that resveratrol extends life span in various organisms, including fish, flies, and yeast, and in mice fed a high-calorie diet. This study found the same effect in obese mice, although they still didn't live as long as mice on a normal diet. Resveratrol had no effect on the life span of animals fed a normal diet, although they had a healthier old age.

It's possible that in this case, the mice didn't begin resveratrol treatment when they were young enough to get the full benefits of the compound, perhaps including a longer life, Sinclair says. Also, unlike humans, mice don't die from cardiovascular disease or suffer serious consequences from brittle bones, so it's possible that resveratrol may be an even greater boon to aging humans than it is to mice, says Rafael de Cabo of the National Institute on Aging, who also worked on the project.

Sinclair's team also monitored gene activity patterns in various tissues in the treated mice and found that they were similar to those in animals on a restricted-calorie diet. Scientists have found that reducing mice's caloric intake by 30 to 50 percent while maintaining adequate nutrition can ward off age-related diseases, improve stress resistance, and slow the declines in function that come with age in many species, including mice, fish, and yeast. Mice treated with resveratrol in this study "have a younger gene-expression profile," de Cabo says.

It's not exactly clear how resveratrol works. There's evidence that the compound activates proteins called sirtuins that play a key role in controlling aging. However, a recent study using lower doses of resveratrol in mice suggests that there may be another mechanism at work, at least when lower doses are given.

The daily dose of resveratrol that Sinclair and his colleagues gave mice was the equivalent of more red wine than most people will drink in a lifetime, so "wine isn't going to do the trick," says Leonard ­Guarente, a professor at MIT and a pioneer in the study of sirtuins. (Guarente is on the board of Sirtris but didn't work on this study.) "There's going to have to be a supplement," he says.

Resveratrol pills are already on the market, but until more studies are done in humans, de Cabo advises caution. Even though you'll get much less of the compound by eating berries and drinking wine, he says, "I'd rather people buy grapes and red wine than take compounds off the shelf."

Sirtris is conducting clinical trials using resveratrol to treat type 2 diabetes. The preliminary results look promising, and no serious side effects have surfaced, notes Sinclair.

He and other scientists are also studying the anti-aging properties of similar compounds--some of them apparently much stronger than resveratrol. "There's a whole pipeline of better molecules coming along," Sinclair says.