Sirt

Sirtuins, abbreviated as SIRTs, are a family of NAD+-dependent enzymes found across bacteria, yeast, plants, and animals. In humans there are seven members, SIRT1 through SIRT7, each with distinct subcellular localizations: SIRT1 and SIRT6 mainly nuclear; SIRT2 primarily cytosolic; SIRT3, SIRT4, and SIRT5 in mitochondria; and SIRT7 in the nucleolus. They regulate transcription, metabolism, DNA repair, mitochondrial function, and responses to cellular stress, with activity tied to cellular NAD+ levels and energy status.

Biochemically, sirtuins catalyze the deacetylation of lysine residues on histone and non-histone proteins, producing nicotinamide and O-acetyl-ADP-ribose. Some members can also catalyze mono-ADP-ribosylation. Through these activities, SIRTs influence chromatin structure and the function of a wide range of substrates.

Key protein targets include transcription factors such as p53, FOXO, and NF-kB, as well as PGC-1α, a regulator of mitochondrial biogenesis. By modulating these and other pathways, sirtuins affect metabolism, stress resistance, aging-related processes, and circadian rhythms.

Therapeutic interest centers on the potential to modulate sirtuin activity for metabolic diseases, neurodegenerative disorders, and cancer. Sirtuin-activating compounds and inhibitors have been explored, but clinical results have been variable, and the efficacy and safety of targeting SIRTs continue to be evaluated in ongoing research.