Resveratrol Rides Again

Ever since scientists learned about the red wine compound resveratrol’s reputed health and antiaging effects, they’ve been debating how the molecule works. The hubbub hinges on whether resveratrol targets sirtuin enzymes, the idea behind the biotech firm Sirtris Pharmaceuticals, which Glaxo­SmithKline purchased for $720 million in 2008. The latest salvo comes from Harvard Medical School’s David A. Sinclair, a Sirtris founder, who for the first time examined what res­veratrol does in mice that lack the sirtuin enzyme SIRT1 (Cell Metab., DOI: 10.1016/j.cmet.2012.04.003). Regular SIRT1 knockout mice die during gestation or have birth defects. So Sinclair’s team developed mice that could have SIRT1 knocked out at adulthood. Resveratrol countered effects of a high-fat diet in normal mice but not in knockouts. However, resveratrol lowered mice’s glucose levels regardless of their sirtuin status. Sirtris stopped drug development of resveratrol because the compound induced kidney problems but continues to develop other sirtuin activators for diseases of aging. The new study doesn’t rule out that resveratrol’s effects on sirtuins are indirect, so “it doesn’t really change anything from my point of view,” say NIH biologist Jay H. Chung, whose work suggests resveratrol directly targets phosphodiesterases rather than sirtuins.