Sirtuin proteins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases. Originally discovered in yeast as gene-silencing proteins, they subsequently emerged as key regulators of life span in yeast and other lower species. Recent identification and characterization of mammalian Sirtuin homologs have revealed a widespread spectrum of biological activities in gene regulation linked to cell survival, cell apoptosis and metabolism. These findings have stimulated several drug discovery efforts. Here, we review current knowledge of the biological functions and possible pharmacological implications of Sirtuin 1, the most characterized member of the mammalian Sirtuin family, in glucose and fat metabolism.
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