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 and lifespan extension. Sirtuins, including SIRT1-7, are human homologs of yeast Sir2p. Sirtuins are NAD+-dependent histone/protein deacetylases (HDAC) which regulate cellular metabolism, e.g. energy metabolism, and thereby are associated with aging and several age-related diseases. SIRT4 localizes to mitochondria, inhibits glutamate dehydrogenase, and is thought to be involved in the regulation of insulin secretion.