NAD-dependent protein deacetylase (Sirtuin) (SIRT)

Sirtuins are a conserved family of NAD+-dependent protein deacetylases that function as key metabolic sensors and regulators of cellular health [PMID: 21385856]. In humans, the family consists of seven members (SIRT1–SIRT7) that reside in various cellular compartments, including the nucleus, mitochondria, and cytoplasm, where they target a diverse range of proteins for deacetylation or other post-translational modifications [UniProt: Q96EB6, Q8IXJ6]. These enzymes are central to the regulation of aging, DNA repair, mitochondrial biogenesis, and stress resistance, often mimicking the physiological effects of caloric restriction [PMID: 22323530]. Because of their broad influence on metabolic and homeostatic pathways, sirtuins are investigated as therapeutic targets for age-related conditions such as type 2 diabetes, Alzheimer's disease, and various cancers [PMID: 23915189]. Drug development efforts focus on both sirtuin-activating compounds (STACs), such as resveratrol and SRT1720, to enhance longevity pathways, and sirtuin inhibitors like selisistat for specific oncogenic or neurological contexts [PMID: 21131905]. Their activity is strictly dependent on the availability of NAD+, linking cellular energy status directly to gene expression and protein function [PMID: 10688192].

Other names

Silent information regulatorSIR2-like proteinClass III histone deacetylaseHDAC Class IIISirtuin family

Sirtuins catalyze the removal of acetyl groups from lysine residues on histone and non-histone protein substrates in a reaction that requires nicotinamide adenine dinucleotide (NAD+), yielding nicotinamide, the deacetylated substrate, and O-acetyl-ADP-ribose [PMID: 10688192].