The Silent Information Regulator (SIR2) family of genes are highly conserved from prokaryotes to eukaryotes and have important functions in the regulation of metabolism, growth and differentiation, inflammation, cellular survival, as well as in senescence, lifespan extension and several age-related diseases. Sirtuins are NAD+-dependent histone/protein deacetylases (HDAC) and SIRT3 is the only sirtuin whose increased expression has been shown to correlate with an extended life span in humans. It is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, including acetyl coenzyme A synthetase 2. SIRT3 is stress-responsive and its increased expression protects myocytes from genotoxic and oxidative stress-mediated cell death.