Scientists have found that the compound resveratrol, found naturally in foods like grapes and nuts, slows age-related deterioration and functional decline of mice on a standard diet, but does not increase longevity when started at middle age.

The findings, published July 3, 2008, in Cell Metabolism, may increase interest in resveratrol as a possible intervention for age-related declines, said NIA scientists. The authors emphasized, however, that their findings are based on research in mice, not in humans, and have no immediate and direct application to people, whose health is influenced by a variety of factors beyond those which may be represented in the animal models.

The study was a collaborative effort between the laboratories of Rafael de Cabo, Ph.D., of the Laboratory of Experimental Gerontology at the NIA; David A. Sinclair, Ph.D., of the Glenn Laboratories for Molecular Biology of Aging at Harvard Medical School; and an international group of researchers. The investigators compared mice fed a standard diet, a high-calorie diet, or an every-other-day feeding regimen with or without high- or low-dose resveratrol to study the impact of resveratrol on aging and health. In previous studies, different forms of dietary restriction, including every-other-day feeding, have been shown to improve markers of health.

“Research is attempting to understand the process of aging and to determine how interventions can influence this process. Dietary restriction has well-documented health benefits in mammals, and the study of possible mimetics of it, such as resveratrol, are of great interest,” said NIA Director Richard J. Hodes, M.D. “Resveratrol has produced significant effects in animal models, now including mice, where it mimics some, but not all, consequences of caloric restriction. Its effects in humans remain to be studied.”

A major finding of the study reported today is that resveratrol prevented age-related and obesity-related cardiovascular functional decline in the mice as determined by several parameters. Total cholesterol was significantly reduced in 22-month-old non-obese mice after 10 months of resveratrol treatment, although triglyceride levels had only a slight, non-significant trend toward a decrease. Further, the aortas of 18-month-old obese and non-obese mice treated with resveratrol functioned significantly better than untreated mice. Resveratrol also moderated inflammation in the heart.

In addition to cardiovascular function, the scientists found resveratrol to have a variety of positive effects on other age-related problems in mice:

* Treated mice tended to have better bone health.
* At 30 months of age, resveratrol-treated mice were found to have reduced cataract formation, a condition found to increase with age in control-group mice.
* Resveratrol enhanced balance and motor coordination in aged animals.
* Resveratrol partially mimicked the effects of dietary restriction on the gene expression profiles of liver, skeletal muscle and adipose (fatty) tissue in mice.

Along with determining the effect of resveratrol on the health of mice, scientists also studied the effect of resveratrol on longevity.

“We found that while quality of life improved with resveratrol, the compound did not significantly affect overall survival or maximum lifespan for mice on a standard diet, compared to mice on the same diet without resveratrol,” reported de Cabo.

Resveratrol did not have a significant effect on lifespan in animals fed standard chow, suggesting that the intervention did not affect all aspects of the basic aging process.

Researchers still have much to learn before resveratrol can be recommended for human use. Basic questions of safety and biological effect in humans remain to be studied experimentally. “We are learning a great deal about how resveratrol affects the health and survival of mammals,” said Dr Sinclair. “Continued study of calorie restriction mimetics such as resveratrol may eventually point the way to new medicines to treat diseases of aging.”

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