Resveratrol's Groundbreaking Effect on Health

The roly-poly mice at one end of David Sinclair's laboratory look the same as the equally fat rodents across the way. While they're sitting still, that is. Place a mouse from each group on a running wheel and the similarity melts away, as one quickly falls off wheezing while the other keeps right on trucking. The sprightlier mouse, in fact, can hold his own against a svelte animal, despite hauling considerable extra body baggage.

In every respect but one, the two fat mice have identical life stories. Both were elderly when subjected to the running test, and both had spent the latter half of their lives on a high-fat diet that led to their plump figures. But along with his food, the champion runner had also received a daily dose of resveratrol, a naturally occurring compound found in red wine. In a study published in the journal Nature, Sinclair and colleagues at Harvard Medical School concluded that resveratrol counteracted the bad effects of overeating, protecting mice from obesity-related diseases and extending their lifespan.

Resveratrol Longevity Studies

Earlier studies had shown that resveratrol increases the lifespan of yeast, fruit flies, roundworms and killifish. Researchers are beginning to think that the compound not only protects from disease but actually slows the aging process. If they are correct, and if the chemical works the same way in humans as it does in mice, longer life may soon be available in pill form.

Sinclair and colleagues compared the health and longevity of three sets of mice. One set was fed a standard diet (SD). The rest of the mice were fed a high-fat diet, in which 60% of their caloric intake was from fat, but half of them were given food spiked with resveratrol.

Sinclair and colleagues set up their study to test the hypothesis that mice fattened on a calorie-rich diet but given resveratrol would, physiologically, come to resemble their leaner kin. To that end, they compared the health and longevity of three sets of mice. One set was fed a standard diet (SD). The rest of the mice were fed a high-fat diet, in which 60% of their caloric intake was from fat, but half of them were given food spiked with resveratrol. (These groups were called HC and HCR-high-calorie and high-calorie + resveratrol.) Because they wanted to test resveratrol's effect on adults, the researchers used mice that were one year old when the study began-middle-aged for mice. The average lifespan of a lab mouse is slightly more than two years.

Resveratrol or no resveratrol, the mice that packed away extra fat and calories bulked up. At 75 weeks of age, they weighed, on average, 40% more than the SD mice. There was no significant difference in weight between the HC and HCR groups.

Mice fattened on a calorie-rich diet but given resveratrol came close to matching the bloodmarkers and tissue health of the slimmer standard diet kin.

But a battery of tests showed that the fat mice were by no means created equal. After only 6 months on the diets, the researchers detected a significant difference in the insulin levels of the HC and HCR mice. Tests of sensitivity to insulin-a measure of how quickly the body clears glucose out of the bloodstream that is an important indicator of diabetes-showed that the HCR mice were much more sensitive than the HC mice. As the researchers had hoped, the mice that received resveratrol scored far closer to the SD group than to the HC group. Other blood markers that indicate diabetes were also much more common among HC than HCR mice. Resveratrol appeared to offer significant protection from diabetes, overcoming the bad effects of poor eating habits.

Next, researchers examined the mice's cells and internal organs. Taking samples from a variety of tissues, including liver, heart and pancreas, the researchers scrutinized cells under the microscope and gave them a rating, from 0-4, based on how damaged they appeared. Visual indicators of tissue health include smooth, intact cell membranes (good) and fat droplets interspersed among cells (bad). The researchers examined all samples blind, meaning that they did not know which group the tissue came from, to ensure that their ratings were not biased. Overall, the average scores were 1.6 for the SD group, 3.2 for the HC group, and 1.2 for the HCR group. In terms of tissue health, resveratrol beat out healthy eating by a nose.

Looking at whole organs, the researchers found that the HC group had grotesquely enlarged livers, a condition often linked to obesity. Livers of the HCR group were small and healthy, essentially indistinguishable from those of the normal eaters. Finally, and perhaps most importantly, preliminary data indicates that resveratrol increases the lifespan of obese, ill-fed mice. The researchers can't give conclusive numbers because some of the mice are still alive, but 58% of mice in the HC group had died by the age of 114 weeks, compared to just 42% in both the HCR and SD groups.

Just two weeks after the Harvard group released its groundbreaking study, a second group of researchers reported findings further bolstering the claim that resveratrol makes fat mice healthier. Johan Auwerx of the University of Strasbourg in France led the study, which found that resveratrol-fed mice on high-fat diets could run twice as far as their unmedicated peers. The study attributed the rodents' impressive performances to an increase in mitochondria, the power plants of the cell. Ordinarily, physical conditioning is the only surefire way to increase the number of mitochondria in cells, but "resveratrol makes you look like a trained athlete without the training," Auwerx told reporters.

Sources

Baur, Joseph A., David Sinclair, et al. "Resveratrol Improves Health and Survival of Mice on a High-Calorie Diet." Nature, November 16, 2006, page 337.

Check, Erika. "A Votre Sant�: Now in Pill Form?" news@nature.com, (November 2, 2006) www.nature.com/ news/ 2006/ 061030/ full/ 444011a.html.

Couzin, Jennifer. "Fountain of Youth for Fat Mice?" ScienceNOW Daily News, (November 1, 2006) sciencenow.sciencemag.org/ cgi/ content/ full/ 2006/ 1101/1.