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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SIRT1
sirtuin 1
Chromosome 10 · 10q21.3
NCBI Gene: 23411Ensembl: ENSG00000096717.12HGNC: HGNC:14929UniProt: A8K128
1,824PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cellular response to hydrogen peroxideregulation of endodeoxyribonuclease activitypositive regulation of proteasomal ubiquitin-dependent protein catabolic processcircadian regulation of gene expressionneurodegenerative diseaseatrial fibrillationtooth diseasehypertension
✦AI Summary

SIRT1 is a highly conserved NAD+-dependent histone deacetylase that functions as a critical regulator of cellular metabolism, aging, and inflammation 1. As the primary enzyme in the sirtuin family, SIRT1 operates by deacetylating both histone and non-histone proteins to modulate gene expression and cellular processes 1. The protein plays a central role in aging-related pathways by regulating key signaling networks including NF-κB, AMPK, mTOR, P53, PGC-1α, and FoxOs 2. SIRT1's deacetylation of PGC-1α is particularly important for metabolic control and mitochondrial biogenesis, linking it to caloric restriction responses and longevity 3. The enzyme also regulates autophagy through deacetylation of FOXOs, ATGs, and LC3, which is crucial during cellular stress conditions 4. SIRT1 expression decreases with aging, while increased expression extends lifespan across multiple species 2. Clinically, SIRT1 alterations are linked to inflammatory diseases, cardiovascular pathologies, neurodegenerative disorders, and diabetic complications 15. The protein shows therapeutic potential, with various nutraceuticals and compounds capable of enhancing SIRT1 activity for treating age-related diseases 67.

Sources cited
1
SIRT1 is an NAD+-dependent deacetylase that regulates inflammation by deacetylating various proteins
PMID: 35359990
2
SIRT1 expression decreases with aging and regulates aging-related signaling pathways including NF-κB, AMPK, mTOR, P53, PGC-1α, and FoxOs
PMID: 32084459
3
SIRT1 deacetylates PGC-1α to regulate metabolic control and mitochondrial biogenesis
PMID: 26831453
4
SIRT1 regulates autophagy through deacetylation of FOXOs, ATGs, and LC3
PMID: 37820856
5
SIRT1 alterations are linked to diabetic kidney disease and other pathological conditions
PMID: 39147198
6
Various nutraceuticals can enhance SIRT1 activity for therapeutic purposes
PMID: 36522127
7
SIRT1 shows therapeutic potential for treating aging-related diseases
PMID: 37499928
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
atrial fibrillationOpen Targets
0.35Weak
tooth diseaseOpen Targets
0.27Weak
hypertensionOpen Targets
0.22Weak
type 2 diabetes mellitusOpen Targets
0.14Weak
chronic obstructive pulmonary diseaseOpen Targets
0.13Weak
SepsisOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
breast cancerOpen Targets
0.12Weak
cancerOpen Targets
0.12Weak
Alzheimer diseaseOpen Targets
0.12Weak
gastric cancerOpen Targets
0.12Weak
gliomaOpen Targets
0.11Weak
Parkinson diseaseOpen Targets
0.11Weak
rheumatoid arthritisOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
nail-patella syndromeOpen Targets
0.11Weak
experimental autoimmune encephalomyelitisOpen Targets
0.11Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
SRT-2104Phase II
NAD-dependent deacetylase sirtuin 1 activator
type 2 diabetes mellitus
Related Genes
FOXO3Protein interaction100%CLOCKProtein interaction100%PPARGC1AProtein interaction100%CCAR2Protein interaction100%FOXO1Protein interaction100%PPARGProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
66%
Ovary
58%
Heart
58%
Liver
36%
Lung
36%
Gene Interaction Network
Click a node to explore
SIRT1FOXO3CLOCKPPARGC1ACCAR2FOXO1PPARG
PROTEIN STRUCTURE
Preparing viewer…
PDB8ANB · 1.64 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.90Intermediate
Observed/Expected LoF0.37 [0.26–0.53]
RankingsWhere SIRT1 stands among ~20K protein-coding genes
  • #63of 20,598
    Most Researched1,824 · top 1%
  • #3,282of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedSIRT1
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Regulation of SIRT1 and Its Roles in Inflammation.
PMID: 35359990
Front Immunol · 2022
1.00
2
SIRT1 and aging related signaling pathways.
PMID: 32084459
Mech Ageing Dev · 2020
0.90
3
Cordycepin Enhances
PMID: 36881089
In Vivo · 2023
0.84
4
The Role of Sirtuin-1 (SIRT1) in the Physiology and Pathophysiology of the Human Placenta.
PMID: 38003402
Int J Mol Sci · 2023
0.82
5
Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis.
PMID: 39199358
Biomolecules · 2024
0.80