Sirtuins are a family of seven NAD+-dependent deacetylase enzymes (SIRT1-7) that regulate metabolism, stress response, and aging. SIRT1 and SIRT3 are most studied.
Mechanism — Remove acetyl groups from histones and other proteins using NAD+ as a cofactor. SIRT1 (nuclear) regulates gene expression and metabolism. SIRT3 (mitochondrial) regulates oxidative phosphorylation. Activated by caloric restriction, exercise, and polyphenols (resveratrol, pterostilbene).
Use case — Support via NAD+ pool maintenance (NMN, NR, niacin), caloric cycling, exercise, polyphenol-rich diet. Direct sirtuin activator supplements (STACs) like resveratrol have human evidence that's underwhelming versus the cellular case.
Caveats — The Sinclair-popularized resveratrol case has been mixed in trials. Sirtuin activity matters; the supplements that claim to activate them are often weak.