National Institutes of Health researchers and their colleagues have identified how resveratrol, a naturally occurring chemical found in red wine and other plant products, may confer its health benefits. The authors present evidence that resveratrol does not directly activate sirtuin 1, a protein associated with aging. Rather, the authors found that resveratrol inhibits certain types of proteins known as phosphodiesterases (PDEs), enzymes that help regulate cell energy. These findings may help settle the debate regarding resveratrol's biochemistry and pave the way for resveratrol-based medicines. The chemical has received significant interest from pharmaceutical companies for its potential to combat diabetes, inflammation, and cancer. The study appears in the February 3, 2012 issue of Cell. "Resveratrol has potential as a therapy for diverse diseases such as type 2 diabetes, Alzheimer's disease, and heart disease," said lead study author Dr. Jay H. Chung, chief of the Laboratory of Obesity and Aging Research at the NIH's National Heart, Lung, and Blood Institute. "However, before researchers can transform resveratrol into a safe and effective medicine, they need to know exactly what it targets in cells." Several previous studies suggested that resveratrol's primary target is sirtuin 1. Dr. Chung and colleagues suspected otherwise when they found that resveratrol activity required another protein called AMPK. This would not be the case if resveratrol directly interacted with sirtuin 1. In the current study, the researchers methodically traced out the metabolic activity in cells treated with resveratrol and identified PDE4 in the skeletal muscle as the principal target for the health benefits of resveratrol. By inhibiting PDE4, resveratrol triggers a series of events in a cell, one of which indirectly activates sirtuin 1.
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