Over the years, wine lovers and more than a few scientists have claimed red wine not only extends the lifespan, but it protects the heart and offers anti-diabetic and anti-cancer effects. Quite a drink! Now, a new study has found that resveratrol, an ingredient in red wine, activates an evolutionarily ancient stress response in human cells, which may be key to increasing longevity and protecting against disease. "With these findings we have a new, fundamental mechanism for the known beneficial effects of resveratrol," said Dr. Mathew Sajish, a senior research associate at the Scripps Research Institute.

The French Paradox

For years, scientists have been puzzled by the so-called “French Paradox,” which refers to the fact that France shows relatively low rates of mortality from coronary heart disease despite how frequently its citizens smoke cigarettes and consume a diet with relatively high levels of saturated fat. Observing this paradox, many scientists have suggested it is the regular and moderate consumption of red wine that might be protecting against cardiovascular disease. (The operative word here is moderate; drinking an excessive amount of alcohol has well-documented negative effects on health.)

So what ingredient in red wine might be beneficial? Resveratrol is a polyphenolic compound found in red wine, grapes, peanuts, cacao beans, Japanese knotweed, and some berries. Resveratrol is produced by these plants in response to stresses, including infection, drought, and ultraviolet radiation. Though resveratrol has been shown to prevent the growth of cancer cells in some animals and it has increased the lifespan of fish and mice fed a high-calorie diet, little is known about the effects of resveratrol in humans. Despite the fact that some of the animal experiments used unrealistically high doses, resveratrol has garnered widespread scientific interest and researchers continue to study the substance, even while they disagree about which signaling pathways it activates.

Activating Longevity Genes

Studies of resveratrol in the early 2000s, for instance, suggested it activates SIRT1, thought to be a longevity gene. However, scientists have begun to question this data. For the current study, Sajish and Dr. Paul Schimmel, senior investigator and member of the Skaggs Institute for Chemical Biology decided to look at what happens to human tyrosyl tRNA synthetase (TyrRS) when resveratrol enters the equation. Because TyrRS translocates to the nucleus under stress conditions, the research team hypothesized that the tyrosine-like phenolic ring in resveratrol might fit, like a jigsaw puzzle piece, into the same binding pocket as TyrRS.

Placing TyrRS and resveratrol together, the researchers showed that resveratrol does indeed mimic tyrosine, which means TyrRS does not perform its usual role in the nucleus — instead, it is steered to a new function. Tracking the resveratrol-bound TyrRS, the researchers discovered that it activates the protein, PARP-1, a major stress response and DNA-repair factor thought to have a significance influence on lifespan. In turn, this activation stimulates a host of protective genes, including a tumor-suppressor gene and longevity genes.

“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.

“We think this is just the tip of the iceberg,” said Schimmel, professor at the Scripps Research Institute. “We think there are a lot more amino-acid mimics out there that can have beneficial effects like this in people. And we’re working on that now.” So while scientists may never solve the age-old riddle — which is tastier, red wine or white wine? — what they may soon discover is exactly how red wine can boost health.

Source: Sajish M, Schimmel P. A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. Nature. 2014.