Harvard Team Unlocks Clues to Genes that Control Longevity

Harvard Medical School Researchers have used a single compound to increase the lifespan of obese mice, and found that the drug reversed nearly all of the changes in gene expression patterns found in mice on high calorie diets–some of which are associated with diabetes, heart disease, and other significant diseases related to obesity.

The research, led by investigators at Harvard Medical School and the National Institute on Aging, is the first time that the small molecule resveratrol has been shown to offer survival benefits in a mammal.

“Mice are much closer evolutionarily to humans than any previous model organism treated by this molecule, which offers hope that similar impacts might be seen in humans without negative side-effects,” says co-senior author David Sinclair, HMS associate professor of pathology, and co-director of the Paul F. Glenn Labs for the Biological Mechanisms of Aging.

“After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice,” said Rafael de Cabo, Ph.D., the study’s other co-senior investigator from the National Institute on Aging’s Laboratory of Experimental Gerontology, Aging, Metabolism, and Nutrition Unit. “There is a lot of work ahead that will help us better understand resveratrol’s roles and the best applications for it.”

Resveratrol is found in red wines and produced by a variety of plants when put under stress. It was first discovered to have an anti-aging properties by Sinclair, other HMS researchers, and their colleagues in 2003 and reported in Nature. The 2003 study showed that yeast treated with resveratrol lived 60 percent longer. Since 2003, resveratrol has been shown to extend the lifespan of worms and flies by nearly 30 percent, and fish by almost 60 percent. It has also been shown to protect against Huntington’s disease in two different animal models (worms and mice).

“The “healthspan” benefits we saw in the obese mice treated with 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,” says Sinclair, who is also a co-founder of Sirtris, a company with an author on this paper and which is currently in a phase 1b trial in humans with diabetes using an enhanced, proprietary formulation of resveratrol. [Harvard has license and equity interests with Sirtris, which is not a public company.]

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