In short
Sirtuins are a family of seven enzymes (SIRT1–SIRT7 in humans) that require NAD+ as a cofactor and regulate processes including DNA repair, gene expression, and mitochondrial function.
Sirtuins remove acetyl groups from proteins (deacetylation) using NAD+ as a required cofactor, which links their activity directly to a cell's NAD+ status. Because NAD+ levels decline with age, sirtuin activity is thought to decline correspondingly, and this connection is a core part of the rationale for NAD+-precursor supplements like NMN and NR.
Different sirtuins have distinct locations and roles: SIRT1 is mostly nuclear and regulates gene expression tied to metabolism and stress resistance; SIRT3 is mitochondrial and regulates mitochondrial enzyme activity and oxidative stress response. In yeast and other simple organisms, extra copies of the sirtuin gene SIR2 extend lifespan, which is the original finding that put this protein family on the aging-research map in the late 1990s.
Resveratrol was popularized as a sirtuin activator following in-vitro and mouse work, but the initial claim that it directly activates SIRT1 was later challenged — some of the original assay results were shown to be artifacts of the fluorescent substrate used, and resveratrol's benefits in mice appear strongest in animals fed a high-fat diet, not standard-diet animals. Human trials of resveratrol have not shown a clear lifespan or robust healthspan benefit, and it should be understood as a compound with a contested mechanism, not a confirmed sirtuin-activating longevity drug in humans.
Worth remembering
- NAD+-dependent enzyme family regulating DNA repair, metabolism, and mitochondrial function.
- Extra SIR2 copies extend lifespan in yeast — the original discovery.
- Resveratrol's status as a direct SIRT1 activator is scientifically contested.