Baur et al., Nature

Livers on a diet.
The livers of mice fed lots of fat along with resveratrol (right) appeared similar to those on a normal diet (left), while animals chowing down extra fat without resveratrol (center) suffered an enlarged organ.

Fountain of Youth for Fat Mice?

A molecule found in grapes and red wine increased the survival rate of fat mice by 30%, according to a new study. The finding comes as scientists hunt ever harder for a holy grail in anti-aging research: An easy-to-take therapy that mimics the long-life benefits of slashing calories, without the unpleasant nature of that drastic diet. It's not clear yet that this treatment is a magic chalice, but the study suggests that the molecule, called resveratrol, is a potent protector of health and life in mammals.

Resveratrol is an antioxidant, a substance that can protect against tissue damage. In the last few years, a team at Harvard Medical School led by molecular biologist David Sinclair has given resveratrol to yeast, flies, and worms, and in every case, the molecule has stretched lifespan (ScienceNOW, 14 July 2004). That's the same outcome scientists have observed for decades in calorie-restricted species (ScienceNOW, 18 January). Researchers have also found that calorie restriction makes a gene called SIR2, or SIRT1 in mammals, more active, which in turn somehow affects metabolism. Sinclair and some others suspect that resveratrol also acts directly or indirectly through SIR2, much like calorie restriction, although other scientists say that hasn't yet been proven.

Following their studies in other species, Sinclair and his colleagues set out to test resveratrol's effects on mice. They studied 1-year-old male mice in three groups of 55 animals each: One was put on a standard diet, a second was fed a high-calorie, high-fat diet, and a third got that same high-calorie diet with daily doses of resveratrol. At 2 years of age, 58% of the animals in the second group were dead of natural causes. In the other two groups, only 42% of the animals had died.

The scientists also found other benefits in the resveratrol group. The motor skills of the animals treated with resveratrol improved as they aged, and they were indistinguishable from the mice on a normal diet. Perhaps most notably, their livers remained healthy, unlike those of obese animals who didn't get resveratrol, the team reports online today in Nature. "The obese mice lived as long and were much more similar to the lean animals," says Sinclair, who has co-founded a company that's designing resveratrol-based treatments. Sinclair is also testing the effects of resveratrol in lean mice and comparing them to calorie-restricted animals.

The results are exciting, says Matt Kaeberlein, a molecular biologist at the University of Washington in Seattle. But he notes that the mice used in the study were inbred, causing them to suffer from just a handful of diseases that typically kill them. It's far from clear whether resveratrol is targeting only those problems or has broader effects, he says. "There's clearly a beneficial effect" of resveratrol, says Cynthia Kenyon, a molecular geneticist at the University of California, San Francisco. She believes it's worth launching a clinical trial testing resveratrol in obese individuals, or those with type 2 diabetes.

Posted in Biology