“Resveratrol extends lifespan”

## What Happened to the Hype David Sinclair's 2003 *Nature* paper showing resveratrol activated SIRT1 and extended yeast lifespan sparked enormous excitement. Follow-up studies showed lifespan extension in nematodes and flies. Then the problems emerged: 1. **Assay artifacts**: A 2010 paper in *Nature Chemical Biology* showed that the SIRT1 activation was only detectable with a fluorescent substrate — a laboratory artifact. SIRT1 activation by resveratrol in physiologically relevant conditions was questionable. 2. **Obese mice only**: Resveratrol extended *sick* (obese) mouse lifespan but did not extend normal-weight mouse lifespan (Pearson et al., *Cell Metabolism*, 2008). 3. **Human pharmacokinetics**: Resveratrol has low bioavailability (~1%) and rapid metabolism. A single glass of wine contains ~100–200 mcg of resveratrol. Animal studies used doses equivalent to hundreds of bottles of wine per day. 4. **Clinical trials**: GlaxoSmithKline acquired Sirtris Pharmaceuticals for $720M in 2008 to develop resveratrol drugs. By 2013, all trials had been discontinued due to lack of clinical benefit and kidney toxicity concerns.