Silent information regulator 2-related enzyme 1 (SIRT1)

Silent information regulator 2-related enzyme 1, commonly known as Sirtuin 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that acts as a master regulator of cellular health and longevity [2, 10]. It functions by removing acetyl groups from both histone tails (e.g., H3K9, H4K16) and a diverse array of non-histone substrates, including p53, NF-kappaB, and PGC-1alpha [8, 14]. Through these deacetylation events, the enzyme modulates critical biological pathways such as energy metabolism, mitochondrial biogenesis, DNA damage repair, and inflammatory responses [3, 9, 13]. SIRT1 is a major therapeutic target for age-related and metabolic disorders, including type 2 diabetes, obesity, and neurodegenerative diseases like Alzheimer's and Parkinson's [9, 10, 12]. In the context of oncology, SIRT1 plays a complex dual role, acting as either a tumor suppressor or a promoter depending on the tissue environment and stage of cancer development [3, 4, 10]. Drug development efforts have focused on both small-molecule activators (STACs), such as resveratrol and SRT1720, and selective inhibitors like selisistat, aimed at treating metabolic syndrome and certain malignancies [10, 14].

Other names

Sirtuin 1SIR2-like protein 1SIR2L1NAD-dependent protein deacetylase sirtuin-1hSIRT1SIR2-alpha

NAD+-dependent deacetylation of histone and non-histone proteins, leading to epigenetic silencing and regulation of transcription factor activity [8, 14].