Low dose Resveratrol slows aging in mammals. Resveratrol outperforms long-term caloric restriction in protecting an aging heart

June 04, 2008

Resveratrol, a major protective polyph cseases include the life-shortening conditions diabetes, heart disease, and cancer.

The study adds to a growing body of research linking Resveratrol to a range of beneficial health effects, including brain and mental health, and cardiovascular health.

Red wine’s Resveratrol has been lauded as the answer to the "French paradox"; why people who live in some regions of France where diets are soaked in saturated fats but washed down with a glass of rouge, paradoxically have a low incidence of heart disease.

Previous in vitro and in vivo studies with Resveratrol suggest that the compound may help prevent the negative effects of high-calorie diets and has anti-inflammatory and anti-cancer potential.

It was thought that you needed very large doses of Resveratrol to obtain life extending, healthspan extending benefits; a costly endeavor with supplements and something totally inappropriate with the copious amounts of red wine needed to achieve sufficient Resveratrol levels. The scientists beg to differ; "Resveratrol is active in much lower doses than previously thought and mimics a significant fraction of the profile of caloric restriction at the gene expression level," said researcher Tomas Prolla from the University of Wisconsin-Madison. In other words, Resveratrol turns on the genes that slow the aging process and protect us from major life threatening disease.

In the animals not fed Resveratrol there were significant changes in the activity of 1,029 genes associated with age in the heart alone. Restricting calorie intake from middle age to old age had a large effect in opposing age related decreased activity in genes reducing the number of genes effected by 90%  or 921 fewer genes affected in the heart) with 536 of these representing highly significant changes (536 were strongly protected). Taking a low dose of Resveratrol changed the number of heart genes affected by aging from 1,029, opposing 947 age related changes in heart genes or decreasing the number of genes affected by aging by a whopping 92%. 522 of the genes were highly significantly protected by the Resveratrol. Thus at doses that can be readily achieved via taking Resveratrol supplements in humans is as effective as caloric restriction in opposing the majority of age-related inefficiencies of gene activity seen in the aging heart. In muscle both caloric restriction and Resveratrol decreased the effect of aging in 26% of the genes affected; of 515 genes that underperformed due to aging 136 of these genes were not affected. In the brain both caloric restriction and Resveratrol decreased the effect of aging on 19% and 13 % of the genes affected by aging respectively.

The new study, published in the open-access journal Public Library of Science One(PLOS 1), suggests that low doses of Resveratrol in the diet of middle-aged mice may influence genes and slow aging and may confer special protection on the heart.

"Our findings that a low dose of Resveratrol partially mimics calorie restriction at the gene expression level and leads to prevention of some age-related parameters suggests that clinical trials with Resveratrol should be conducted to test the relevance of these findings to humans," wrote lead author Jamie Barger from LifeGen Technologies in Wisconsin.

"Because cardiac disease is a major contributor to age-related mortality, positive findings could lead to a novel and important approach to improve the quality of human life."

The researchers fed middle-aged mice (14-months) a control diet, a low dose of Resveratrol (4.9 mg kg per day), or a calorie restricted (CR) diet, and followed the animals until old age (30 months). They found that animals in the calorie-restriction and low-dose Resveratrol groups had altered gene expression profiles in the heart associated with prevention of the decline in heart function associated with ageing. In short, a glass of wine or food or supplements that contain even small doses of Resveratrol are likely to represent "a robust intervention in the retardation of cardiac ageing," wrote the authors.

"There must be a few master biochemical pathways activated in response to caloric restriction, which in turn activate many other pathways," said Prolla. "And Resveratrol seems to activate some of these master pathways as well."

The work of the Wisconsin team was funded by the National Institutes of Health and DSM Nutritional Products of Basel, Switzerland. The study is published in the June 4th, 2008 issue of the journal PLOS-One