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Sirtuin family of proteins (SIRT (used collectively for family; specific members are SIRT1, SIRT2, ... SIRT7))
- Target
- SIRT (used collectively for family; specific members are SIRT1, SIRT2, ... SIRT7)
- Molecular classification
- Enzyme, Class III histone deacetylase, Epigenetic regulator, NAD+-dependent deacetylase, Metabolic regulator
01
Overview
The sirtuin family of proteins comprises seven NAD+-dependent enzymes in humans (SIRT1–SIRT7), homologous to the yeast Sir2 protein. These enzymes act as class III histone deacetylases and play integral roles in chromatin remodeling, gene expression, DNA repair, cellular metabolism, and response to oxidative stress. Sirtuins are highly conserved across species, function in both the nucleus and cytoplasm, and are deeply involved in the regulation of aging, inflammation, and metabolic processes. As therapeutic targets, sirtuins are being intensely studied for their roles in cancer, cardiovascular disease, neurodegenerative disease, and other disorders, with several drugs under investigation designed to modulate their activity for clinical benefit[2][3][4][5].
- Other names
- SIRT proteinsSilent information regulator proteinsSir2 family proteins (homology reference to yeast Sir2)
02
Mechanism of action
Activation or inhibition of sirtuin enzymatic activity (deacetylation of histone/non-histone proteins) Modulation of transcription factor activity Alteration of cellular stress response pathways Regulation of longevity and metabolic signaling
03
Biological functions
Epigenetic gene silencingChromatin remodeling and modificationRegulation of gene expressionDNA maintenance and repairMitochondrial biogenesisCellular energy metabolismCell cycle regulationApoptosisOxidative stress responseInflammation modulation
04
Disease associations
CancerCardiovascular diseaseNeurodegenerative diseaseInflammatory disordersMetabolic disease (diabetes, obesity)Aging-related disorders
05
Safety considerations
Off-target effects due to broad biological roles of sirtuinsPotential for altering critical cellular processes, leading to unwanted effects such as impaired apoptosis or excessive cell survivalLong-term suppression or enhancement may have consequences on aging or cancer riskDose dependence and specificity for individual SIRT family members remain key therapeutic challenges
06
Interacting drugs
Resveratrol
6 more in the full profile.
07
Biomarkers
SIRT protein expression levels (especially SIRT1) in tissue or circulationNAD+ levels (as a cofactor essential for sirtuin activity)SIRT1 activity assaysChanges in acetylation status of SIRT1 substrates (e.g., p53, PGC-1α)
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