Thursday, November 02, 2006

A Life-Extending Pill for Fat Mice

A compound found in red wine keeps obese mice healthy and extends their life span.

By Katherine Bourzac

Resveratrol, a compound found in red wine, extends the healthy life span of obese mice. Credit: Istockphoto\Tomasz Sowinski

A compound found in red wine keeps middle-aged mice on a high-fat, high-calorie diet as healthy as mice on a healthy diet, according to research at the National Institute on Aging and Harvard Medical School.

The compound, called resveratrol, also improves the mice's survival rates, extending them to the same lengths as those of mice on a healthy diet. These preliminary results may demonstrate resveratrol's ability to activate molecular pathways thought to be critical regulators of the aging process. Indeed, the researchers say the mouse study is the first demonstration in mammals of the activation of known genetic pathways affecting life span by a drug--a good sign for researchers and pharmaceutical companies that hope to treat the diseases of aging by developing drugs that intervene in these pathways.

Human obesity is associated with a higher risk of diabetes and heart disease, and of age-related diseases such as cancer. Mice on a high-fat, high-calorie diet have similar problems: the control group in this study exhibited elevated blood levels of glucose and insulin (early signs of diabetes), fatty livers, unhealthy hearts, relatively poor motor coordination, and changes in gene-expression patterns that correlate with unhealthy diets.

Treating mice on such an unhealthy diet with resveratrol starting in middle age appeared to alleviate the negative health effects of obesity, although the mice did not lose weight. They have healthy livers and hearts, and their insulin sensitivity is comparable to that of mice on a healthy diet, as are their motor skills. And "most amazingly," says Rafael de Cabo, a head researcher on the project and also a researcher in gerontology at the National Institute on Aging, resveratrol reverses almost all of the diet-induced changes in gene expression--changes that may contribute to heart disease, cancer, and other maladies.

While the life-extending effects of resveratrol have previously been demonstrated in yeast, roundworms, fruit flies, and fish, this is the first comprehensive demonstration of the compound's health benefits in mice. The mice in the study are currently 27 to 28 months old; their life expectancy is 32 to 36 months, and time will tell whether resveratrol increases the maximum life span of the mice on the high-fat diet. However, according to research published in the journal Nature, the survival rates of the resveratrol-treated mice on the high-fat diet are comparable to those of mice on a normal diet (at 114 weeks old, 42 percent of both groups had died), while more mice in the high-fat, no-treatment group have died (at 114 weeks old, 58 percent had died).

"Overall, the results are quite striking," says Richard Weindruch, professor of medicine at the University of Wisconsin-Madison, who studies the effects of low-calorie diets on life span and health (see "The Fountain of Health" and "Do Dieting Monkeys Live Healthier and Longer Lives?"). He says the study demonstrates "a rather remarkable effect of resveratrol to oppose a highly toxic diet."

There have been some previous scientific reports of the beneficial health effects of red wine and resveratrol supplements in humans. "This was not a molecule we just pulled off the shelf," says David Sinclair, the associate professor of pathology at Harvard who headed the study with de Cabo. Sinclair's previous research has demonstrated that in yeast, resveratrol extends life span, and that it activates a gene called Sir2, a master regulator of aging in these organisms. The mouse study takes the next step, says Sinclair, asking, "Is there any hint [that] resveratrol can improve health in mammals?"