NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

NAD-dependent protein deacetylase sirtuin‑1 is a highly conserved enzyme that catalyzes the removal of acetyl groups from lysine residues in histones and various non-histone proteins using NAD+ as a cofactor. This post-translational modification regulates chromatin structure and gene expression but also affects diverse cellular processes including metabolism, stress responses, autophagy induction, cell survival/apoptosis balance, DNA repair mechanisms, inflammation control and organismal aging. As a central epigenetic regulator linking nutrient sensing to transcriptional programs that govern healthspan and lifespan across species—from yeast Sir2 to human SIRT1—it is widely considered an important therapeutic target for age-associated diseases such as cancer neurodegeneration cardiovascular disorders metabolic syndrome inflammatory conditions among others.

Other names

Sirtuin 1SIR2L1 (Silent information regulator 2-like protein 1)SIR2 homolog 1Silent mating type information regulation 2 homolog 1 (S. cerevisiae)

Drugs targeting SIRT1 typically act by either activating or inhibiting its NAD+-dependent deacetylase activity. Activators enhance the removal of acetyl groups from lysine residues on target proteins—modulating transcription factors such as p53 or FOXO—and thereby influence cellular metabolism, stress resistance, autophagy, inflammation suppression, or longevity pathways. Inhibitors block this activity to increase acetylation levels on these substrates.