Page last updated: Tuesday, November 18, 2008
Resveratrol shown to mimic calorie restriction by Phil Norrie
Molecules found in red wine, peanuts and other products of the plant world have for the first time been shown to mimic the life-extending effects of calorie restriction, a finding that could help researchers develop drugs that lengthen life and prevent or treat aging-related diseases.

Resveratrol, was shown in a study to extend the life span of yeast cells by up to 70%. Howitz et al report the discovery of three classes of small molecules that activate sirtuins,showing that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending life-span by 70%. The researchers discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators. David Sinclair, an assistant professor of pathology at Harvard Medical School, said he and his fellow researchers hope the molecules will prove to prolong life not just in yeast but in multi-cellular organisms like worms, fruit flies and, perhaps, humans.

Sinclair said the study may help explain why moderate consumption of red wine has been linked to lower incidence of heart disease and why resveratrol prevents cancer in mice. Scientists know that putting organisms on a calorie-restricted diet reduces the incidence of age-related illnesses such as cancer, osteoporosis and heart disease. In the 1990s, research showed that single genes can control how fast organisms age. Scientists have been racing to find ways of manipulating those genes by finding molecules that activate the enzymes that in turn influence the genes that regulate aging. Sinclair’s team screened thousands of molecules to see which ones might activate the enzymes.They found a group of 18 molecules, resveratrol being just one, and all of them came from plants and were produced in response to harsh environmental conditions like drought.To illustrate that theory, Sinclair noted that red wines from regions with harsher growing conditions- Spain, Chile, Argentina and Australia- contain more resveratrol than those produced where grapes are not highly stressed or dehydrated.

Professor R. Curtis Ellison comments ‘We have a huge amount of direct data in humans on the effects of alcohol and wine in preventing disease, especially the diseases associated with aging, such as heart disease, stroke, osteoporosis, and Alzheimer’s Disease. If anyone wants to base public policy on research, it should at least be based on studies in humans (not studies in worms, fruit flies, and mould!). The vast amount of interest in this paper is because it raises the possibility that some companies can isolate a single substance from wine (or other matter) and make a big profit from putting it into a capsule.

I believe that there are probably hundreds of active substances in wine other than resveratrol that have healthy properties. And it is probably the resveratrol in conjunction with many other substances, especially the alcohol, that will turn out to be the healthiest "drug" we should be taking. St. Leger, Cochrane and Moore published a classic paper in 1979 describing the inverse association between the average per capita wine consumption of a country and its mortality rates of coronary disease (Lancet 1979;1:1017-1020). These authors ended their paper by stating: "If wine is ever found to contain a constituent protective against I.H.D. (ischemic heart disease, or coronary disease) then we would consider it almost a sacrilege that this constituent would be isolated. The medicine is already in a highly palatable form."

SOURCE: Howitz KT et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003.

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