Resveratrol shows activity against insulin resistance and retinal disease

Anti-aging compound appears to function in multiple ways

A naturally occurring chemical found in grapes and other foods may help reverse some of the ills associated with aging and being overweight, new studies suggest.

The chemical, resveratrol, has been shown to lengthen the life span of yeast and improve health in laboratory animals, but scientists do not yet know whether the substance might also benefit humans.

Two new studies of older or overweight people suggest that it can, by helping boost the action of insulin. And a study in mice shows that the chemical works through a previously unknown mechanism to halt harmful blood vessel growth in the retina.

As people age or gain weight, their ability to respond to insulin declines. Some people become mildly resistant to insulin’s action, so that their muscles and other tissues no longer take up and burn glucose efficiently. That condition, known as insulin resistance, is one of the first steps toward diabetes. Now, researchers have found that resveratrol improves the response to insulin in overweight people with insulin resistance and older people with mild insulin resistance. The older people in the study were an average age of 72.

People in the two studies took supplements containing resveratrol at concentrations much higher than are found in food “or even several bottles of wine,” says Jill Crandall, an endocrinologist at the Albert Einstein College of Medicine in New York City. “We’re encouraged by these results, but do have to stress that they are preliminary.” Crandall presented the results of the two studies in Anaheim, Calif., June 27 and June 28 at a meeting of the American Diabetes Association.

“The benefits [of resveratrol] are unproven and the risks seem minimal, but haven’t been formally tested,” Crandall says. She and her colleagues also don’t know how resveratrol may be working in the body to boost the response to insulin.

Resveratrol has previously been shown to stimulate the activity of proteins known as sirtuins, which have been linked to longer life and better regulation of metabolism in laboratory animals. But a new animal study indicates that resveratrol may work through other biological processes to stop blood vessels from invading the retina and causing blindness associated with eye diseases such as macular degeneration, or retinopathies caused by diabetes or premature birth.

Resveratrol inhibited blood vessel growth in the retinas of mice that had injuries to their eyes caused by lasers, a new study appearing in the July issue of the American Journal of Pathology shows. Resveratrol was able to stop blood vessel growth even when researchers inactivated the sirtuin proteins, indicating that the chemical’s effect on blood vessel growth must work by another mechanism.

That mechanism turns out to be a biological process involving a protein known as elongation factor-2 kinase, says Rajendra Apte, a retinal surgeon at Washington University School of Medicine in St. Louis, who led the study.

Other researchers have suspected that resveratrol may do its work through more than just sirtuins (SN: 8/2/08, p. 14), but the new study provides some of the first evidence that resveratrol may take multiple pathways toward improving health.

If Apte’s results hold up in clinical trials, resveratrol might one day be used in conjunction with current therapies against advanced stages of macular degeneration, says Jerry Niederkorn, an ocular immunologist at the University of Texas Southwestern Medical Center at Dallas. “It looks like this could deliver a one-two punch” in conjunction with other therapies, says Niederkorn, who was not involved in the research.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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