Resveratrol is a plant-derived polyphenol that extends lifespan and healthspan 
in model organism. Despite extensive investigation, the biological processes 
mediating resveratrol's effects have yet to be elucidated. Because repression of 
translation shares many of resveratrol's beneficial effects, we hypothesized 
that resveratrol was a modulator of protein synthesis. We studied the effect of 
the drug on the H4-II-E rat hepatoma cell line. Initial studies showed that 
resveratrol inhibited global protein synthesis. Given the role of the mammalian 
Target of Rapamycin (mTOR) in regulating protein synthesis, we examined the 
effect of resveratrol on mTOR signaling. Resveratrol inhibited mTOR 
self-phosphorylation and the phosphorylation of mTOR targets S6K1 and eIF4E-BP1. 
It attenuated the formation of the translation initiation complex eIF4F and 
increased the phosphorylation of eIF2α. The latter event, also a mechanism for 
translation inhibition, was not recapitulated by mTOR inhibitors. The effects on 
mTOR signaling were independent of effects on AMP-activated kinase or AKT. We 
conclude that resveratrol is an inhibitor of global protein synthesis, and that 
this effect is mediated through modulation of mTOR-dependent and independent 
signaling.