Prof comments on red wine anti-aging link

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Friday, November 17, 2006

Red wine – or at least one component of it – may hold the key to combating aging and disease in the future, according to a report that was the topic of a Nov. 2 article in the journal Nature.

“This is a great sign of progress for the future of the field,” said Professor of Biology Stephen Helfand, who studies the process of aging using fruit flies as a model. “The data at the moment are incredibly exciting,” he added, though he cautioned that “everything has to be looked at again and re-tested.”

The study, which was conducted at Harvard University, tested the effect of resveratrol, a substance found in red wine, on the health and lifespan of mice. The results showed that resveratrol reduces the negative effects of a high-calorie diet in mice and drastically extends lifespan, according to David Sinclair, the Harvard researcher who led the study along with Harvard professor Joseph Baur and Rafael de Cabo, an investigator at the National Institute on Aging.

Sinclair’s team compared the general health and lifespans of three groups of mice, one of which was fed a high-calorie diet supplemented with resveratrol. The other two groups received either a high-calorie diet or a normal diet without resveratrol, according to the Nov. 2 Nature article. The mice fed high-calorie food had greater rates of obesity, cardiac and liver disease and a metabolic condition very similar to diabetes. These mice also tended to die at younger ages than mice with normal caloric intakes.

Those mice that received the high-calorie diet along with a large dose of resveratrol gained the same amount of weight as the other high-calorie group but did not exhibit many of the negative effects associated with the non-resveratrol group.

The non-resveratrol high-calorie group showed higher rates of liver and cardiac disease as well as higher blood glucose levels than the group of mice assigned to a high-calorie diet and resveratrol. More strikingly, the mice given resveratrol had around the same lifespan as those fed a regular diet.

“(Resveratrol) seems to reverse the negative health effects tied to a high-calorie diet,” Helfand said.

Helfand said scientists have known since the 1930s about the positive effects of calorie reduction on the health and lifespans of a variety of species. Theoretically, a significantly reduced caloric intake could also increase lifespan and improve general health in humans as well, he added.

“There are obvious problems to calorie reduction for humans, though,” Helfand said. “Mainly that you are hungry all the time.” Resveratrol seems to mirror the effect of dramatic calorie reduction without the unpleasantness of hunger, he added.

Helfand’s work in the field of aging also involves trying to determine the way radical calorie reduction affects certain genes, such as SIRT-1.

According to the Nature article, the possible mechanism for resveratrol’s effect in the study is the chemical’s activation of SIRT-1, which also is activated by radical calorie reduction.

“By understanding the way radical calorie reduction works, we can find pharmacological ways to mimic its effect,” Helfand said.

It is this application to medicine that excites researchers most about resveratrol’s effect on physical deterioration caused by excessive calorie intake. If it works as well on humans as it does on mice, resveratrol could potentially be an effective preventative measure against such deterioration, Helfand said.

While there are some limitations to the usefulness of non-human subjects, “the fact that resveratrol seems to help diverse species, from yeast to flies to, now, mice,” supports the generality of the result, Helfand said, adding that the ability of researchers to manipulate genes in species like fruit flies and mice make them ideal test subjects.

The mechanism at work in resveratrol is not well understood in mice or humans, Helfand said. It is also unclear what effects might come with long-term exposure to the high doses of resveratrol required to drastically increase lifespan and general health.

Also, the Nature article notes, mice receiving resveratrol still suffered from obesity and elevated cholesterol levels.

“Right now, it looks too good to be true,” Helfand said. “People will jump on the bandwagon only to find it may not do everything it is supposed to … but hopefully people will have the perseverance to keep looking for ways this could help.”

“There is still a long way to go (in aging research),” said Josh Waitzman ’07, a biophysics concentrator who conducts independent research on aging in Helfand’s lab.

“Aging research now … is untangling how everything is interconnected, piece by piece, and putting it back together again,” Waitzman said. “It’s really exciting.”

Sirtris Pharmaceuticals, a company co-founded by Sinclair, is seeking to develop substances that mimic the effects of resveratrol, but with smaller doses, according to the company’s Web site.

Sinclair and his team’s report did not recommend supplementing one’s diet with resveratrol before safety trials are conducted. Sinclair, however, takes a small daily dose of the substance, which is currently available in some dietary supplements, according to a Nov. 2 article in the New York Times.