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Summary
Sirtuin proteins were once only of interest to yeast geneticists studying transcriptional regulation. That changed when their conserved effects on extending life span in yeast, worms, and flies were reported (1–3). Attention widened even more at the possibility of small-molecule activators of sirtuins increasing human health span and perhaps also life span (see the figure). Then came resveratrol, a natural compound found in red wine that could reportedly activate SIRT1, a human member of the sirtuin family. But just as quickly as red wine became the toast of the town, the biochemical assays used to identify resveratrol and other sirtuin-activating compounds (STACs) were called into question. Speculation that the cellular effects of STACs are achieved not through direct SIRT1 binding, but instead through other proteins, gave pause to wine enthusiasts, among others. Glasses may be lifted once again, however. On page 1216 of this issue, Hubbard et al. (4) demonstrate that SIRT1 can indeed be activated by resveratrol and other STACs in vitro, but only under certain conditions.
