Sirtuin enzyme (SIRT (individual family members: SIRT1, SIRT2, ..., SIRT7))

Sirtuin enzymes (SIRTs) are a conserved family of **NAD+-dependent deacetylases** and ADP-ribosyltransferases that regulate the **acetylation state of histones and numerous non-histone substrates**. In mammals, the family includes seven homologs (SIRT1–7) localized to different cellular compartments (nucleus, cytoplasm, mitochondria). Sirtuins modulate fundamental cellular processes, including gene expression, DNA repair, stress response, aging, apoptosis, and metabolism, largely by removing acyl modifications from lysine residues of target proteins. Their activity is tightly coupled to cellular NAD+ levels, linking them to metabolic state. Sirtuins have diverse substrate specificities and play critical roles in cancer, neurodegenerative diseases, metabolic disorders, and aging. Both small molecule inhibitors and activators of sirtuins are under active development for a range of therapeutic indications[2][3][4][5][7][9].

Other names

Sir2-like proteinSirtuin deacetylaseNAD+-dependent deacetylase

Inhibitors: block the NAD+-dependent deacetylase activity, altering acetylation state of histones and transcription factors Activators: enhance deacetylase activity, promoting deacetylation of specific substrates and downstream gene expression changes