CAMBRIDGE, Mass., July 3, 2008 -- Sirtris, a GlaxoSmithKline company focused on discovering and developing small molecule drugs to treat diseases of aging such as Type 2 Diabetes, is included among a research team that reported in today's online edition of Cell Metabolism that mice treated at middle-age to the end-of-life with resveratrol showed an overall health improvement, including improved bone health, a reduction in cataracts and cardiovascular dysfunction, and improved balance and motor coordination.
Resveratrol probably works by mimicking the effects of calorie restriction. The big advantage of resveratrol is that most people can't stand to live in constant hunger. Taking a pill is a whole lot easier.
"In this study, we wanted to determine whether or not resveratrol, which imparts many of the same health benefits as caloric restriction in mice, does so by inducing a physiology similar to dietary restriction," says study co-author David Sinclair, Ph.D., a Sirtris co-founder and Harvard Medical School Associate Professor of Pathology. "The data show that resveratrol does induce many similar pathways," says Sinclair, who is co-chair of Sirtris' Scientific Advisory Board. The study was co-led by Rafael de Cabo, Ph.D. at the National Institute on Aging and David Sinclair.
The research team began testing of mice at one year, the mouse equivalent of middle-age, as that is when a small molecule drug mimicking dietary restriction might be given to humans.
Rather than restricting calories by feeding the mice less per day the researchers restrictd calories with every-other-day feeding (EOD). Anyone know why?
The mice were placed on different diets: a standard diet (SD); every-other-day feeding (EOD); and a high-calorie diet (HC). Mice in each dietary regime were divided into treated and untreated subgroups, with some not receiving resveratrol and others receiving different dosage levels of resveratrol.
Surprisingly, resveratrol extends life of those on the calorie restriction diet. I say "surprisingly" because calorie restriction is already causing most of the changes that resveratrol causes. But note that mice on the middle range calorie diet did not live longer as a result of resveratrol treatment.
The study showed that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by dietary restriction, a diet known to slow aging and extend lifespan in rodents and dogs. The study also found a significant increase in lifespan in both the resveratrol treated group on a high-calorie diet and the resveratrol treated group on a calorie restriction diet, but the treatments did not extend lifespan of mice on a standard diet when started at one year of age. This study was funded by the National Institute on Aging.
Maybe on the EOD mice the resveratrol worked by mimicking the effects of calorie restriction on the feeding days?
Resveratrol altered mitochondrial gene expression. I like the idea of delaying osteoporosis, cataracts, and decline in motor coordination.
Specifically, researchers found that resveratrol decreased functional decline often seen in the frail and elderly, such as osteoporosis, cataracts, and motor coordination. For example, in general, femurs from the resveratrol-treated mice trended toward better bone properties, suggested that resveratrol could reduce age-induced bone loss in normal mice. Cataract formation was also lessened by resveratrol in a dose-dependent manner. The mice on a SD treated with resveratrol also showed a significant improvement in balance and motor coordination. The resveratrol treated mice also had improved markers for cardiovascular health. Their arteries were more youthful, and they had reduced aortic stiffness. They also had fewer free radicals and DNA damage.
Even better, I like the idea of reversing the aging process so that we never get osteoporosis, cataracts, cancer, heart disease, decline in motor coordination, shriveling of muscles, graying of all hair, hearing problems, loss of teeth, knee pain, wrist pain, and a great many other things that make aging very undesirable.
My reaction to this study is mild disappointment. Resveratrol did not work nearly as well as calorie restriction in extending life. You still need to starve yourself to assure a longer life.
Resveratrol did not have a significant effect on lifespan in animals fed standard chow, suggesting that the intervention did not affect all aspects of the basic aging process. Mice on a high-calorie diet without resveratrol lived the shortest length of time and mice on an every-other-day regimen lived the longest, regardless of resveratrol treatment. However, for mice on a high-calorie diet, mean and maximum lifespan increased for mice on resveratrol when compared with the control mice. Researchers found that resveratrol's effects on longevity could be completely uncoupled from changes in body weight, meaning that mice on a high-calorie diet with resveratrol did not necessarily lose weight but did experience a longer (and healthier) life than mice on the same high-calorie diet not taking resveratrol. They speculate that improved cardiovascular health and reduced fatty changes in the liver may have contributed to the increased lifespan of resveratrol-treated mice.
I'm still not taking resveratrol yet. But this result makes me lean a little closer toward taking it.
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