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Listening to Resveratrol

Could the famous ingredient of red wine herald a new era in medicine?

David Kent

In my Cambridge, Massachusetts, neighborhood, competing restaurants have promoted opposing gastronomic and life strategies. The motto at Jae's, a "nouvelle" Pan-Asian café specializing in presenting small, stylized foods on oversized white plates, was "Eat at Jae's. Live forever!" The sign next door at Jake and Earl's take-out grill read "Eat BBQ. Die Happy!" Although neither establishment survived long, the stark choice that together they presented-between a savory, greasy gluttony and a long life-conforms to some deeply rooted and more enduring puritanical logic.

Aged%20hurdle-jumper%20with%20red%20wineClick to Enlarge Image Indeed, until recently the only approach researchers had found to effectively extend lifespan—whether in a single-celled organism or a mammal—was through severe caloric restriction. Countless people have accordingly taken up caloric-restriction diets in the hope that it will work in humans too. Though this tactic is unproven, my friends who have tried it assure me that, at the very least, their lives will certainly seem longer. Biotechnology, however, presently promises to offer us a more palatable means of attaining a longer life than perpetual semi-starvation.

Caloric deprivation appears to slow aging through the activation of members of a family of enzymes called sirtuins, which belong to a larger group called deacetylases. These enzymes appear to reduce cell death by protecting cells against reactive oxygen species and DNA damage. Perhaps the most seminal work in this area came from David A. Sinclair's laboratory at Harvard, which described a group of compounds, including resveratrol (famously in red wine), that stimulate the activity of sirtuins across a variety of species. Resveratrol also has been found to increase lifespan in a variety of laboratory animals, including simple worms, fruit flies and short-lived fish. More recently, Sinclair and his colleagues reported that resveratrol can improve health and survival in mice fed a high-calorie diet (perhaps of Jake and Earl's BBQ).

Not surprisingly, these findings led to a spike in the sale of red wine (which apparently has such small amounts of active resveratrol as to be biologically inert at drinkable doses) as well as over-the-counter nonalcoholic wine-derived dietary supplements (of variable activity). In order to develop and bring to market more potent-and patentable-alternatives, Sinclair helped to create a company, called Sirtris. In June of this year, only four years after it was founded, Sirtris was bought by the pharmaceutical giant GlaxoSmithKline for a tidy $720 million. Who can doubt that commercially available life-extending compounds are around the corner? Even if the effects in humans are less dramatic than those of resveratrol in yeast (60 percent increase in replicative lifespan) or than in the overfed mouse (15 percent increase in lifespan), it seems that we are on the cusp of a dramatic shift in medicine, one for which we may not be fully prepared. 



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