Sirtuins are a family of seven mammalian enzymes, SIRT1 through SIRT7, that remove acetyl and other acyl groups from lysine residues. Their defining feature is chemical: unlike class I/II histone deacetylases, they require NAD+ as a co-substrate and consume one NAD+ per deacylation, releasing nicotinamide and 2'-O-acyl-ADP-ribose. That stoichiometry makes sirtuin activity directly sensitive to cellular NAD+ supply.
Why sirtuins matter
Each family member has its own compartment and substrate set: SIRT1 and SIRT6/7 are largely nuclear and act on histones and transcription factors including PGC-1alpha, p53 and FOXO; SIRT3, SIRT4 and SIRT5 sit in mitochondria, where SIRT3 deacetylates enzymes of fatty-acid oxidation and the electron transport chain; SIRT2 is mainly cytoplasmic and acts on tubulin. This is the mechanistic bridge that links NAD+ precursors such as NMN to the transcriptional and mitochondrial endpoints reported in ageing models.
Findings should be read carefully. The early yeast and invertebrate lifespan claims for Sir2 were substantially revised after replication attempts, and reports that resveratrol activates SIRT1 directly were complicated by assay-fluorophore artefacts. Contemporary work leans on genetic models and on NAD+ availability rather than on direct small-molecule activation.
Related terms and material
AMPK · senolytic · preclinical. Reference material: NAD+, spermidine, longevity peptides. Further reading: peptides for anti-aging research.