Glossary
Sirtuin
The seven sirtuins, SIRT1 to SIRT7, strip acyl groups from proteins using NAD+, each in its own compartment. Roles, and why NAD+ levels set their activity.
The sirtuins are seven mammalian enzymes, SIRT1 to SIRT7, that remove acetyl and related acyl marks from lysines. What sets them apart is their chemistry: unlike the class I/II HDACs, they consume NAD+ as a co-substrate and use up one NAD+ for every deacylation, liberating nicotinamide and 2’-O-acyl-ADP-ribose. Because of this one-to-one stoichiometry, sirtuin activity responds directly to how much NAD+ the cell has.
Locations and targets
Every member has its own location and set of substrates: SIRT1 and SIRT6/7 are mostly nuclear and modify histones and regulators like FOXO, p53 and PGC-1alpha; SIRT3, SIRT4 and SIRT5 reside in mitochondria, where SIRT3 acts on respiratory-chain proteins and on beta-oxidation enzymes; SIRT2 sits largely in the cytosol and acts on tubulin. Here lies the mechanistic bridge between NAD+ precursors like NMN and the gene-expression and mitochondrial readouts reported in ageing research.
Interpret the literature with care. Early lifespan claims for Sir2 in yeast and invertebrates were considerably revised once replication was attempted, and reports of resveratrol directly activating SIRT1 were muddied by artefacts from the assay fluorophore. Today the field leans on knockout and transgenic models and on NAD+ supply rather than on small-molecule activators.
Related terms and material
See also senolytic, preclinical and AMPK. In the shop: NAD+, spermidine and the longevity range; our overview covers peptides in anti-aging research.