Resveratrol

Resveratrol’s chemical structure gives it the ability to activate the sirtuin gene. This gene is important in suppressing DNA instability and allowing for repair of damaged DNA. One of the known causes of aging is the decreased ability for older cells to perfectly replicate DNA in every new cell. The build up of “DNA debris” in cells is connected to aging and the death of individual cells. Resveratrol increases the rate of deacetylation, which controls whether a gene is turned on or off. By controlling the rate of deacetylation and activating the sirtuin gene, resveratrol is demonstrated to have longevity effects.

In 2008, researchers at Harvard Medical School and the National Institute of Aging, led by Sinclair and Cabo, compared mice fed with different forms of dietary restriction, with or without high or low dose resveratrol. The aim was to study the impact of resveratrol on aging and health. It was a follow-up study to one conducted in 2006 which found that resveratrol improves the health and longevity of overweight, aged mice. They found that as with previous results, resveratrol prevented age-related and obesity-related cardiovascular decline in the mice and moderated inflammation in the heart. Resveratrol also had a variety of positive effects on other age-related problems in mice. It enhanced balance and motor coordination and reduced cataract formation. Furthermore, mice treated with resveratrol tended to have better bone health, as measured by thickness, volume, mineral content and density, and bending stiffness. The findings of the study with regard to longevity were not as positive. Researchers observed that resveratrol did not significantly affect overall survival or maximum lifespan for mice which were fed the drug. They concluded that there is still much to learn before resveratrol can be recommended for human use.

It was previously believed that only high resveratrol doses are effective in increasing SIRT1 activity, thereby prolonging life or slowing the effects of age-related diseases. However, a study published in Experimental Gerontology in 2008 reported that a much lower resveratrol dose (100 mg human equivalent of trans-reveratrol, 4 to 320 times lower than in previous studies) caused a 9-fold greater genomic effect than plain resveratrol or a calorie-restricted diet. Another study found that mild to moderate expression of SIRT1 when administered to mice slowed down aging of the heart, whereas a high dose of SIRT1 induced cardiomyopathy. In addition, high levels of SIRT1 increased oxidative stress, whereas moderate expression induced resistance to oxidative stress and apoptosis. Researchers suggested that SIRT1 could retard aging and increase stress resistance to the heart in vivo, but only at low to moderate doses (up to 7.5-fold).