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An Intervention That Dramatically Slows Aging and Age-Related Diseases in Mammals

Resveratrol has been shown to mimic the beneficial effects of caloric restriction in mice, but it’s far too early to recommend the use of resveratrol supplements in humans.

Every animal ages: Vitality flags, and eventually death comes. Aging has seemed both inevitable and immutable. Yet, for 70 years, we have known that severe restriction of caloric intake can extend the vitality and lifespan of many animals.

About 15 years ago, armed with new molecular biological tools, investigators began the search to identify the biochemical changes that connect caloric restriction to vitality. Enzymes called sirtuins — present in all animals, including humans — appear to be important. Three years ago, resveratrol, a molecule produced in plants, was found to activate sirtuins just as caloric restriction does and thereby extended the lifespan of yeast (Journal Watch Sep 23 2003). Resveratrol has also been shown to enhance vitality and to extend lifespan in fruit flies, worms, and a species of fish.

Recently, a multi-institutional team reported the first results on resveratrol in mammals (Journal Watch Nov 9 2006). The team randomized middle-aged mice to a standard diet (SD), a high-calorie, high-fat diet (HC), or a high-calorie, high-fat diet plus resveratrol (HCR). As expected, the HC mice steadily gained weight and developed decreased insulin sensitivity, reduced motor function, increased liver size and fatty liver, fatty lesions and inflammation in heart muscle, and reduced numbers of hepatic cell mitochondria. They also died at a significantly younger age than the other mice. In marked contrast, HCR mice (which also gained weight) did not undergo these biochemical or pathologic changes. Moreover, they were as active as, and lived as long as, SD mice. A second study in mice, just published online, found that resveratrol greatly increased the aerobic capacity of mice by inducing genes for oxidative phosphorylation and mitochondrial biogenesis (Cell 2006 Nov 15).

Aging — as well as atherosclerosis, diabetes, and many age-related neurologic diseases — increasingly is being linked to diminished cellular capacity for oxidative phosphorylation and number of mitochondria. These studies and others report that resveratrol improves both measures, protects against insulin resistance and diabetes, and improves cognition in mice. Like the mice in these studies, many of us are middle-aged mammals on high-calorie, high-fat diets. That is why these results are profoundly exciting. However, because resveratrol’s value in humans has not been proved, and its manufacture is unregulated, use of resveratrol supplements cannot be encouraged — at least not now.

— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine December 28, 2006