Sirtuin 1 (SIRT1)

Sirtuin 1 (SIRT1) is a highly conserved NAD+-dependent histone deacetylase that belongs to the Sirtuin family, often referred to as the Sir2 family after its yeast homolog. It acts as a master metabolic sensor, linking cellular energy levels (via NAD+ availability) to the regulation of gene expression and protein function. SIRT1 deacetylates a broad range of substrates, including histones and key transcription factors such as p53, NF-κB, and PGC-1α, thereby controlling processes like apoptosis, inflammation, mitochondrial biogenesis, and DNA repair. Due to its central role in cellular homeostasis and longevity, SIRT1 is a major therapeutic target for age-related conditions, including type 2 diabetes, neurodegenerative diseases, and cardiovascular disorders. Pharmacological strategies include the development of sirtuin-activating compounds (STACs) to mimic the benefits of calorie restriction and inhibitors for specific oncogenic contexts. However, its dual role as both a tumor suppressor and a potential promoter in advanced cancers presents a significant challenge for drug development.

Other names

NAD-dependent protein deacetylase sirtuin-1SIR2L1SIR2hSIR2SIR2-like protein 1Silent information regulator 2 homolog 1Sir2 family

SIRT1 functions as an NAD+-dependent deacetylase that removes acetyl groups from lysine residues on both histone and non-histone proteins. This deacetylation activity regulates the function of key transcription factors and enzymes involved in metabolism, stress response, and cell survival. Drugs targeting SIRT1 act as either sirtuin-activating compounds (STACs) that enhance its catalytic activity or as inhibitors that block its active site [6, 8, 16].