~ 060708 Low Dose Resveratrol Gets To The Heart Of Longevity

An article published on June 4, 2008 in the online journal Public Library of Science (PLoS) ONE supports earlier findings of a beneficial effect for resveratrol on the genetic changes that occur with aging. Previous research utilizing resveratrol, which is found in grapes, pomegranates and other foods, demonstrated that the compound prevented early mortality when administered in large doses to mice given high fat diets. The current study's results provide evidence of a cardioprotective benefit for resveratrol at a relatively low dose.

Researchers at the University of Wisconsin-Madison and the University of Florida fed middle-aged (14 month old) rats a control diet, a diet containing a small amount of resveratrol, or a calorie restricted diet until the animals were 30 months of age. The team found similarities between the genetic effects of calorie restriction and those of resveratrol in the heart, skeletal muscle and brain. While the expression of 1,029 heart genes changed with age in the control animals, calorie restriction was found to reduce 90 percent, and resveratrol reduced 92 percent, of these age-related alterations in expression.

"Thus, resveratrol at doses that can be readily achieved through dietary supplementation in humans is as effective as calorie restriction in opposing the majority of age-related transcriptional alterations in the aging heart," the authors write. "Because the collection of such alterations in gene expression is a biomarker of aging, our results imply that similar to calorie restriction, middle-age onset resveratrol supplementation at low doses is likely a robust intervention in the retardation of cardiac aging."

"Resveratrol is active in much lower doses than previously thought and mimics a significant fraction of the profile of caloric restriction at the gene expression level," explained senior author and UW professor of genetics Tomas Prolla. "There must be a few master biochemical pathways activated in response to caloric restriction, which in turn activate many other pathways. And resveratrol seems to activate some of these master pathways as well."

"This brings down the dose of resveratrol toward the consumption reality mode," added senior author Richard Weindruch, who is a professor of medicine at the University of Wisconsin-Madison. "At the same time, it plugs into the biology of caloric restriction."

A clinical trial is scheduled to take place at the University of Florida to test resveratrol's benefits in older individuals. The study will evaluate the compound's effects on inflammation, physical performance, memory and oxidative damage.

Related Health Concern: Calorie restriction

Caloric restriction is the most effective and well-documented pathway to longevity in animal studies. Both the mean and maximum life spans of yeast, rotifers, water fleas, nematodes, fruit flies, spiders, fish, hamsters, rats, mice, and dogs have been extended significantly by decreasing normal caloric consumption by 30 percent to 40 percent (Weindruch R et al 1988).

When calorie restriction with optimal nutrition (CRON) is begun in young animals, they remain smaller and leaner than their free-feeding counterparts (Weindruch R et al 1988). They also withstand a number of stressors better than their free-feeding counterparts (Berg TF et al 1994; Heydari AR et al 1993; Masoro EJ 1998).

Increased life span in yeast can be induced by adding resveratrol, an antioxidant found in red wine, to their growth medium. These results have been replicated in both worms (Caenorhabditis elegans) and pomace flies (Drosophila melanogaster) (Wood JG et al 2004), suggesting that the action of resveratrol may be equivalent to that of caloric restriction. Whether resveratrol will prove to be a caloric restriction agent in mammals, primates, and humans remains to be seen.

Recent studies at the BioMarker Pharmaceuticals laboratory have shown that a nutrient formula from the Life Extension Foundation that contains extracts of grape seed and skin, a whole red grape resveratrol extract, vitamin C, and calcium (from calcium ascorbate) can produce many of the gene expression effects found in mice on CRON. Studies funded by the Life Extension Foundation at the Chinese Academy of Sciences in Beijing have shown that this formula can improve the strength and coordination of pomace flies (D melanogaster) afflicted with a motor disorder that is similar to Parkinson's disease in humans. This formula can protect mitochondria (the energy-generating power plants in the cell) isolated from rat livers from damage caused by exposure to carcinogens.

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