Sirtuin family NAD+-dependent deacetylases (SIRTs)

The Sirtuin family consists of seven NAD+-dependent deacetylases (SIRT1–7) that serve as critical metabolic sensors, linking cellular energy status to various biological processes. These enzymes remove acetyl groups from both histone and non-histone proteins, thereby regulating gene expression, DNA repair, and mitochondrial function (UniProt, 2023). SIRT1 is the most extensively characterized member, known for its roles in promoting longevity and protecting against metabolic stress by targeting proteins like p53 and PGC-1alpha (PubMed, PMC4944358). In disease, sirtuins are implicated in the pathogenesis of neurodegeneration, type 2 diabetes, and cardiovascular disorders, often showing protective effects when activated (NIH, 2021). Conversely, their role in cancer is complex, acting as either tumor suppressors or promoters depending on the context and isoform (StatPearls, 2023). Pharmacological modulation of sirtuins, particularly through Sirtuin Activating Compounds (STACs) like resveratrol and synthetic analogs, remains a major area of drug development for age-related diseases (PubChem, 2024).

Other names

Silent information regulator proteinsClass III histone deacetylasesSIR2-like proteinsSirtuinsNAD-dependent protein deacetylases

Sirtuins catalyze the deacetylation of lysine residues on histone and non-histone proteins in a reaction that requires NAD+, yielding nicotinamide and O-acetyl-ADP-ribose. Drugs act as either Sirtuin Activating Compounds (STACs) to enhance this activity, often by lowering the Km for the substrate, or as inhibitors to block deacetylation in specific disease contexts like cancer.