Chemical Genetic Approach Confirms Metabolic Benefits of Sirt1.

By activating SIRT1, the red wine polyphenol, resveratrol, was purported to imitate life-prolonging aspects of caloric restriction, including induction of mitochondrial biogenesis, reduction of inflammation and protection against metabolic decline. Dr. David Sinclair of Harvard Medical School and international colleagues have now demonstrated resveratrol improves skeletal muscle mitochondrial function and induces a shift toward more oxidative muscle fibers in wild-type mice fed a high-fat diet, but has no effect on tamoxifen-inducible SIRT1 knockout mice fed the same diet (Price et al, Cell Metab. 2012;15(5):675-90). Additionally, overexpression of SIRT1 in transgenic mice mimicked the effects of resveratrol. The studies provide convincing evidence that SIRT1 is a critical player in orchestrating the effects of resveratrol on mitochondrial biogenesis and the switch to more oxidative muscle fibers.

Enzo Life Sciences has played a pioneering role in HDAC and sirtuin drug discovery efforts, offering the most comprehensive portfolio of small molecule modulators, recombinant proteins, antibodies and assay kits relevant to elucidating the roles of Sirt1 in metabolism and disease.

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