Scientists have known for some time that drastically reducing calorie intake prolongs the lives of a wide variety of organisms. But the molecular mechanisms underlying this phenomenon have proved difficult to discern. Recent studies have indicated that a natural enzyme known as Sir2 mediates longevity in yeast, worms and rats. Findings published online today by the Proceedings of the National Academy of Sciences indicate that the same holds true in fruit flies.
To explore the effect of Sir2 in the fruit fly Drosophila, Blanka Rogina and Stephen Helfand of the University of Connecticut obtained flies that were genetically engineered to produce more or less of the enzyme than normal. Flies that made more Sir2 lived as much as 57 percent longer than the normal span of a few weeks. But cutting their food supply in half didn't extend their lives any further. This and other tests suggest that calorie reduction prolongs life only by raising Sir2 levels. The long-lived flies appeared to have the same "quality of life" as normal flies, as judged by how active and fertile they were.
Molecular biologists have become accustomed to seeing the same cellular machinery reused by many different species. Still, finding similar molecules at work in calorie restriction is intriguing, because what eventually causes death in yeast, worms, flies and rats is completely different. David Sinclair of Harvard Medical School, who has studied Sir2 in yeast, where it acts to stabilize DNA, says that the enzyme may be part of an ancient system for responding to stress.
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Scientists are searching for drugs that might capture the life prolonging benefits of extreme diets by directly stimulating Sir2 production. Indeed, Rogina, Helfand and Sinclair contributed to a paper published earlier this year in Nature that showed that fruit flies and nematodes live longer when exposed to resveratrol, an antioxidant found in red wine that raises Sir2 levels. Determining whether resveratrol has a similar effect in such long-lived species as humans, however, will take many years.