Sirtuin
Family of NAD+-dependent protein deacetylases that regulate metabolism, stress response, DNA repair, and longevity.
For laboratory and research use only — not for human consumption.
Sirtuins (named for the founding yeast member Sir2 — silent information regulator 2) are a family of seven mammalian NAD⁺-dependent protein deacetylases (SIRT1 through SIRT7) that regulate metabolism, stress response, DNA damage repair, and longevity through deacetylation of histone and non-histone substrates. SIRT1 (nuclear, cytoplasmic) and SIRT6 (nuclear) are the most-studied longevity-related family members; SIRT3, SIRT4, and SIRT5 are mitochondrial. SIRT1 substrates include the transcription factors FOXO1/3 (driving stress-response and autophagy programmes), p53 (modulating apoptosis), PGC-1α (driving mitochondrial biogenesis), and the histone H3K9, H3K14, and H4K16 marks (regulating chromatin state). SIRT3 deacetylates numerous mitochondrial enzymes including the manganese-dependent superoxide dismutase, supporting anti-oxidant defence. The sirtuin–NAD⁺ axis is the molecular substrate of the caloric-restriction longevity phenotype: caloric restriction raises cellular NAD⁺ availability, activating sirtuin-mediated programmes that improve mitochondrial function, autophagic flux, and cellular stress resistance. In peptide longevity research, the sirtuin axis is a downstream readout for compounds proposed to support cellular ageing biology — including epitalon (reported telomerase upregulation may be partly sirtuin-mediated) and the mitochondrial peptides Humanin, MOTS-c, and SS-31. Pharmacological sirtuin activators (resveratrol, NMN/NR via the NAD⁺ pathway) remain the dominant small-molecule approach.