NAD-dependent protein deacetylase sirtuin-1 (SIRT1) (SIRT1)

NAD-dependent protein deacetylase sirtuin-1 (SIRT1) is a critical metabolic sensor and class III histone deacetylase that regulates diverse cellular processes by removing acetyl groups from lysine residues on both histone and non-histone proteins [1][4]. As its activity is dependent on nicotinamide adenine dinucleotide (NAD+), it acts as a link between the metabolic state of the cell and the regulation of gene expression and protein function [5][18]. SIRT1 influences key physiological pathways including glucose and lipid metabolism, mitochondrial biogenesis, DNA repair, and the inflammatory response by targeting essential transcription factors such as p53, PGC-1α, and NF-κB [4][13][20]. Its ability to promote longevity and enhance metabolic efficiency has made it a significant therapeutic target for age-related conditions, including type 2 diabetes, neurodegenerative disorders like Alzheimer’s disease, and cardiovascular diseases [10][11][13]. Pharmacological strategies involve the use of sirtuin-activating compounds (STACs) such as resveratrol and synthetic small molecules to treat metabolic and inflammatory diseases, while SIRT1 inhibitors are being investigated for their potential to sensitize cancer cells to chemotherapy [10][25].

Other names

Sirtuin 1SIR2L1SIR2hSIR2SIR2-like protein 1Silent information regulator 2-like protein 1Silent mating type information regulation 2 homolog 1

Sirtuins utilize nicotinamide adenine dinucleotide (NAD+) as a co-substrate to remove acetyl groups from lysine residues on histones and various transcription factors (such as p53, PGC-1α, and NF-κB), yielding nicotinamide, 2'-O-acetyl-ADP-ribose, and a deacetylated substrate protein [1][5][9].