Red Wine Compound May Extend Life

- Resveratrol, a polyphenol found in red wine, extended survival rates of mice and prevented the negative effects of high-calorie diets, says a new study published in Nature.

The study, described by an independent expert as potentially “the breakthrough of the year”, adds to a growing body of research linking resveratrol and red wine consumption to a range of beneficial health effects, including brain and mental health, and cardiovascular health.

"The "healthspan" benefits we saw in the obese mice [fed] resveratrol, such as increased insulin sensitivity, decreased glucose levels, healthier heart and liver tissues, are positive clinical indicators and may mean we can stave off in humans age-related diseases such as type 2 diabetes, heart disease, and cancer, but only time and more research will tell," said co-author David Sinclair from Harvard Medical School.

The new study, published on-line in Nature (doi: 10.1038/nature05354), looked at the effects of the feeding middle-aged mice (52 weeks old) one of three diets: a standard mouse diet, a high calorie (fat) diet and a high calorie (fat) diet supplemented with resveratrol.

At 60 weeks of age, the researchers report that the survival curves of the high calorie and the high calorie/resveratrol groups began to diverge, with the resveratrol group showing a 3-4 month advantage in survival.

When the mice reached ‘old age' (114 weeks), lead author Joseph Baur and his colleagues report that more than 50 per cent of the high calorie mice had died compared to less than 33 per cent of the high calorie mice receiving resveratrol.

Baur reported that the high calorie mice (no resveratrol supplement) were found to have increased plasma levels of insulin, glucose and insulin-like growth factor (IGF) 1 - markers that in humans predict the onset of diabetes - when compared with their overweight counterparts supplemented with resveratrol.

Pathological studies of the heart tissues of mice from the three diet groups showed that the abundance of fatty lesions, degeneration and inflammation were significantly less for the standard diet and resveratrol-supplemented group (1.6 and 1.2 points on a relative scale of 0-4), compared to the high calorie diet group (3.2 points).

"After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet," said Rafael de Cabo, Ph.D., from the National Institute on Aging (NIA).

The mechanism behind the apparent benefits is proposed to be related to activation of an enzyme called SIRT1. To determine this, they looked at the amount of a specific chemical modification (acetylation) on the molecule PGC-1alpha. The research team found that levels of PGC-1alpha were three-fold lower in the resveratrol-supplemented mice than in the high calorie mice, consistent with what would be expected when SIRT1 was being activated by resveratrol, they said.

“This study shows that an orally available small molecul at doses achievable in humans can safely reduce many of the negative consequences of excess caloric intake, with an overall improvement in health and survival,” concluded the researchers.

While the results are very promising, Richard Hodes, M.D., director of the NIA, added a note of perspective and caution: "At the same time, it should be cautioned that this is a study of male mice, and we still have much to learn about resveratrol's safety and effectiveness in humans."

Professor Steve Bloom, an obesity researcher at Imperial College, London, told the BBC: "If we start with the idea that there is an evolutionary advantage for the life expectation of each species, and this is tied into scarcity or abundance of food.

"If there is plenty of food, you'll live a very active life for a while, and then drop dead. If there isn't much food, because reproduction takes more energy, it is better to keep a small number of animals going for longer.

"There is a system to regulate it, and it looks like resveratrol bypasses this system or may be an endogenous part of that system.

"This paper is extremely interesting - it could be the breakthrough of the year, with massive possibilities for… human beings."

In an accompanying article (Nature, doi:10.1038/nature05308), Matt Kaeberlein and Peter Rabinovitch, from the University of Washington, said: "The safety of resveratrol at the high doses in humans comparable to those used by [the researchers] is unknown, especially over the course of years or even decades, when relatively modest side-effects could have dramatic consequences."

"For now, we counsel patience. Just sit back and relax with a glass of red wine - which alas, has only 0.3 per cent of the relative resveratrol dose given to the gluttonous mice," they said.

The amount of resveratrol in a bottle of red wine can vary between types of grapes and growing seasons, and can vary between 0.2 and 5.8 milligrams per litre. But nearly all dark red wines – merlot, cabernet, zinfandel, shiraz and pinot noir – contain resveratrol.