Scientists at The Scripps Research Institute (TSRI) have found that a fundamental new mechanism for the known beneficial effects of resveratrol — the grapes and red-wine ingredient once touted as an elixir of youth: it powerfully activates an evolutionarily ancient stress response in human cells. “This stress response represents a layer of biology that has been largely overlooked, and resveratrol turns out to activate it at much lower concentrations than those used in prior studies,” said senior investigator Paul Schimmel, professor and member of the Skaggs Institute for Chemical Biology at TSRI. The discovery is reported in Nature. Resveratrol is a compound produced in grapes, cacao beans, Japanese knotweed and some other plants in response to stresses including infection, drought and ultraviolet radiation. It has attracted widespread scientific and popular interest over the past decade, as researchers have reported that it extended lifespan and prevented diabetes in obese mice and vastly increased the stamina of ordinary mice running on wheels. More recently, though, scientists in this field have disagreed about the signaling pathways resveratrol activates to promote health, questioning some of resveratrol’s supposed health benefits.
…The first studies of resveratrol in the early 2000s had suggested that it exerts some of its positive effects on health by activating SIRT1, also thought to be a longevity gene. But SIRT1’s role in mediating resveratrol’s reported health-boosting effects has been questioned lately. The team’s experiments showed, however, that the TyrRS-PARP-1 pathway can be measurably activated by much lower doses of resveratrol — as much as 1,000 times lower — than were used in some of the more celebrated prior studies, including those focused on SIRT1. “Based on these results, it is conceivable that moderate consumption of a couple glasses of red wine (rich in resveratrol) would give a person enough resveratrol to evoke a protective effect via this pathway,” Sajish said. He also suspects that effects of resveratrol that only appear at unrealistically high doses may have confounded some prior findings.