An evolutionary ancient stress response in human cells is activated powerfully by resveratrol, an ingredient present in red wine, reveals a new study.
Scientists at The Scripps Research Institute (TSRI) said that the finding should dispel much of the mystery and controversy about how resveratrol really works.
Senior investigator Paul Schimmel, professor and member of the Skaggs Institute for Chemical Biology at TSRI said that 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.
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.
Earlier study had begin to find hints that a tRNA synthetase called TyrRS, which links the amino acid tyrosine to the genetic material that codes for it, can move to the cell nucleus under stressful conditions-apparently taking on a protective, stress-response role. Sajish noted that resveratrol appeared to have broadly similar stress-response properties and also resembled TyrRS's normal binding partner tyrosine.
The new study put TyrRS and resveratrol together and showed with tests including X-ray crystallography that resveratrol does indeed mimic tyrosine, well enough to fit tightly into TyrRS's tyrosine binding pocket.
That binding to resveratrol, the team found, takes TyrRS away from its protein translation role and steers it to a function in the cell nucleus.
Tracking the resveratrol-bound TyrRS in the nucleus, the researchers determined that it grabs and activates the protein, PARP-1, a major stress response and DNA-repair factor thought to have a significance influence on lifespan. The scientists confirmed the interaction in mice injected with resveratrol. TyrRS's activation of PARP-1 led, in turn, to the activation of a host of protective genes including the tumor-suppressor gene p53 and the longevity genes FOXO3A and SIRT6.
The study was published in Nature.