Small molecule, big controversy. A new study clears doubts about how resveratrol causes its anti-aging effects.

Resveratrol, the famed anti-aging supplement extracted from red wine, has experienced its share of controversy. An experimental artifact, a pair of studies that questioned its health benefits, and the shady practices of one now-discredited scientist have put resveratrol in a bad light as of late. But a recent study now attempts to help set the record straight by confirming one part of the resveratrol puzzle.

Resveratrol was first identified in 2003 when Konrad Howitz, working with David Sinclair's group at Harvard, found that it activated the protein SIRT1. Past research has “implicated” SIRT1 as an anti-aging factor due to the beneficial effects it has on glucose homeostasis, neurodegeneration, and integrity of the cell’s power house, the mitochondria. A number of studies suggested that the healthful benefits of resveratrol were via the activation of SIRT1 but it still remained to be shown convincingly. Even casting doubt on resveratrol's ability to activate SIRT1 were two 2005 studies that showed that a fluorescent marker used in one of the experiments was activating SIRT1 itself.

To get to the molecular bottom of things, Harvard biologist David Sinclair and his team devised an elegant experiment to see if resveratrol still had the same effect on cells if SIRT1 was removed. This would be a convincing demonstration that the beneficial effects of resveratrol were indeed through the activation of SIRT1. To do this the group developed a mouse that was genetically modified so that all of the SIRT1 in its body would disappear when it was given a certain chemical. Strikingly, normal mice in the study reaped the expected benefits when given resveratrol, but mice with no SIRT1 did not.

Sinclair co-founded Sirtis Pharmaceuticals, which is developing drugs that, like resveratrol, activate SIRT1, so obviously data supporting that the benefits of resveratrol are via SIRT1 activation helps out Sinclair and other companies developing drugs meant to mimic resveratrol or otherwise activate SIRT1. Conversely, we previously pointed out that two studies which put into question resveratrol’s beneficial effects were performed by Pfizer and Amgen, companies in competition with Glaxo-Smith-Kline who bought Sirtis in 2008 for $720 million.

Does the potential conflict of interest detract from the powerful demonstration Sinclair’s team was able to show with their genetically-modified mice?  There are sure to be more pieces to the resveratrol puzzle and the current experiment will have to be reproduced. But for the moment, demonstrating the link between the wine extract and SIRT1 is an important step if resveratrol will ever be shown to live up to its anti-aging potential.

[image credits: LA Times and extremelongevity.net]
images: wine and molecule

Peter Murray was born in Boston in 1973. He earned a PhD in neuroscience at the University of Maryland, Baltimore studying gene expression in the neocortex. Following his dissertation work he spent three years as a post-doctoral fellow at the same university studying brain mechanisms of pain and motor control. He completed a collection of short stories in 2010 and has been writing for Singularity Hub since March 2011.