Sci. Aging Knowl. Environ., 14 July 2004
Resveratrol to the Rescue
Compound that boosts yeast longevity also benefits worms and flies
A yeast is a worm is a fly is a person? At least the first three creatures live longer when they sup an extract of red wine, according to new research. The chemical activates related enzymes in all three organisms and might duplicate the effects of extreme dieting. By showing for the first time that the compound works in animals, the results bring human studies a step closer.
Extra copies of the SIR2 gene stretch life span in yeast--measured by how many times a cell reproduces--and in nematodes (see Kaeberlein Perspective). The Sir2 protein belongs to a family of proteins called sirtuins that also appear in humans and other animals, and researchers wonder whether sirtuins also prolong our lives. In a study that thrilled the wine industry, molecular geneticist David Sinclair of Harvard Medical School in Boston and colleagues reported last year that the sirtuin-stimulator resveratrol, a component of red wine, lengthened life in yeast cells (see "Raise a Glass to Long Life"). Those results were promising, says Sinclair, "but let's face it, it's only a fungus." The researchers wanted to test resveratrol on creatures more closely related to humans.
The team measured whether resveratrol and several related compounds goad sirtuins from flies and nematodes. Most of the chemicals increased the activity of proteins from both species; for example, resveratrol more than doubled the productivity of Drosophila sirtuin. The researchers then showed that resveratrol prolongs worm life span by about 14%. Wrigglers that lacked a functional Sir2 equivalent didn't gain time over controls, supporting the hypothesis that the chemical works by sparking sirtuins. Resveratrol and the kindred molecule fisetin also bought extra days for fruit flies--boosting their life span by as much as 29%.
Calorie restriction, or drastically reduced food intake, can also prolong life in many organisms (see Masoro Review). The researchers reasoned that if the bugs lived long because they were going hungry, they would produce fewer eggs. But flies on resveratrol squeezed out extra eggs, suggesting that they eat plenty. When the researchers slashed rations, the flies lasted no longer if they also slurped resveratrol, hinting that the compound and calorie restriction extend longevity through the same pathway. The study is the first to show that the molecule can stretch life span in more complex organisms, Sinclair says. The group has begun testing the compound in rodents.
The yeast results were provocative, but to advance toward human studies, "it was crucial to show that resveratrol is having a similar effect in animals," says molecular geneticist Stewart Frankel of the University of Hartford in Connecticut. Molecular biologist Leonard Guarente of the Massachusetts Institute of Technology says that the study "makes it increasingly likely that Sir2 will be universal in regulating diet and life span." Scientists now need to sort out how resveratrol rouses sirtuins and determine whether our cells make similar activators, says biochemist John Denu of the University of Wisconsin, Madison. Such knowledge could help researchers design more potent compounds to stimulate sirtuins, he says. We might soon know whether we can join the list of resveratrol's beneficiaries.
July 14, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150