gene

SIRT1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about SIRT1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

3093Connections
13Hypotheses
13Analyses
50Outgoing
50Incoming
11Experiments
16Debates

Summary

SIRT1 is a gene implicated in neurodegeneration research. Key relationships include: activates, regulates, associated with. Associated with ALS, ALZHEIMER'S DISEASE, Aging. Connected to 1385 entities in the SciDEX knowledge graph.

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🧬 Gene Info
Gene SymbolSIRT1
Chromosome10q21.3<br>
Target ClassEpigenetic Regulator
FunctionSIRT1 uses NAD+ as a cofactor, linking its activity to cellular energy status and metabolic health.
Mechanism of ActionSIRT1 activation via NAD+ precursors or allosteric activators deacetylates tau (reducing aggregation), enhances mitophagy, and restores circadian gene expression
DruggabilityMedium (0.48)
Clinical StagePhase III
PathwaysAkt, Ampk Signaling, Angiogenesis, Apoptosis, Autophagy
UniProt IDQ96EB6
NCBI Gene ID23411
Ensembl IDENSG00000096717
GeneCardsSIRT1
Human Protein AtlasSIRT1
Associated Diseasesaging, aging-related diseases, Als, Alzheimer
Known Drugs/Compoundscurcumin, DSS, EDARAVONE, Ginsenoside Re, intermittent fasting, kaempferol
InteractionsACAT1, ACETYL-COA, ACOX1, ACTB, Actin, ACVR1
SciDEX TargetView Target Profile (6 clinical trials)
SciDEX HypothesesNutrient-Sensing Epigenetic Circuit Reactivation
SIRT1-Mediated Reversal of TREM2-Dependent Microgl
Astrocyte Metabolic Memory Reprogramming
KG Connections3093 knowledge graph edges
DatabasesGeneCardsHPASTRING
🔮 Predicted Structure: SIRT1 — AlphaFold Q96EB6 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (6)

Knowledge base pages for this entity

Canonical Page

SIRT1 Gene

gene · 1038 words

Epigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor

idea · 3877 words

SIRT1 Signaling Pathway in Alzheimer's Disease

pathway · 2490 words

SIRT1 Activators for Parkinson's Disease

mechanism · 1622 words

SIRT1 Protein

protein · 1592 words

SIRT1 (Redirect)

redirect · 593 words

Pathway Diagram

graph TD
    SIRT1["SIRT1"] -->|"promotes"| AUTOPHAGY["AUTOPHAGY"]
    SIRT1["SIRT1"] -.->|"inhibits"| OXIDATIVE_STRESS["OXIDATIVE_STRESS"]
    SIRT1["SIRT1"] -->|"activates"| autophagy["autophagy"]
    SIRT1["SIRT1"] -->|"promotes"| autophagy_1["autophagy"]
    SIRT1["SIRT1"] -->|"associated"| Tumor["Tumor"]
    SIRT1["SIRT1"] -->|"associated"| Parkinson["Parkinson"]
    QBA["QBA"] -->|"activates"| SIRT1["SIRT1"]
    LACTATE["LACTATE"] -->|"activates"| SIRT1["SIRT1"]
    AMPK["AMPK"] -->|"activates"| SIRT1["SIRT1"]
    METFORMIN["METFORMIN"] -->|"activates"| SIRT1["SIRT1"]
    style SIRT1 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1763)

TargetRelationTypeStr
Canceractivatesdisease1.00
INFLAMMATIONtherapeutic_targetgene1.00
Alsexpressed_indisease1.00
Alsactivatesdisease1.00
AGINGactivatesgene1.00

Incoming (1330)

SourceRelationTypeStr
ROSactivatesgene1.00
INFLAMMATIONactivatesgene1.00
NADregulatesgene1.00
NADassociated_withgene1.00
OXIDATIVE STRESSactivatesgene1.00

Targeting Hypotheses (13)

Hypotheses where this entity is a therapeutic target

HypothesisScoreDiseaseAnalysis
Nutrient-Sensing Epigenetic Circuit Reactivation 0.907 neurodegeneration Epigenetic reprogramming in aging neuron
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc 0.895 neurodegeneration Gene expression changes in aging mouse b
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt 0.824 neurodegeneration View
NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic A 0.790 neurodegeneration epigenetic reprogramming aging neurons
SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resil 0.778 neurodegeneration How do gut microbiome-derived metabolite
H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from E 0.770 neurodegeneration Investigate mechanisms of epigenetic rep
TREM2-SIRT1 Metabolic Senescence Circuit in Microglial Aging 0.744 neurodegeneration Gene expression changes in aging mouse b
NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogram 0.700 neurodegeneration What molecular mechanisms drive microgli
LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation 0.666 neurodegeneration Does LRRK2's role as a lysosomal volume
Astrocyte Metabolic Memory Reprogramming 0.646 neurodegeneration How do astrocyte-neuron metabolic intera
NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/ 0.602 neurodegeneration View
NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Compl 0.592 neurodegeneration test
SIRT1-Mediated Epigenetic Restoration of MFSD2A Expression R 0.498 neuropharmacology What determines blood-brain barrier pene

Mentioning Analyses (13)

Scientific analyses that reference this entity

Investigate mechanisms of epigenetic reprogramming in aging neurons

neurodegeneration | 2026-04-10 | 0 hypotheses

Can circadian interventions reverse microglial priming independent of sleep disr

chronobiology | 2026-04-08 | 0 hypotheses

Epigenetic reprogramming in aging neurons

neurodegeneration | 2026-04-04 | 9 hypotheses Top: 0.914

Senescent cell clearance as neurodegeneration therapy

neurodegeneration | 2026-04-04 | 7 hypotheses Top: 1.000

How do neurodegeneration gene expression patterns in SEA-AD differ from other po

neurodegeneration | 2026-04-04 | 2 hypotheses Top: 0.611

Experiments (11)

Experimental studies targeting or related to this entity

ExperimentTypeDiseaseScoreFeasibilityModelStatusEst. Cost
Gandouling protection against brain injury in Wilson's disease via SIR validation Hepatolenticular degeneration 0.900 0.00 TX mice (Wilson's disease mode proposed N/A
Irisin effects on osteogenic differentiation in mesenchymal stem cells exploratory bone fracture 0.900 0.00 mouse bone mesenchymal stem ce proposed N/A
PGC-1α knockout analysis of PV+ interneuron maturation validation neurodevelopmental disorders 0.850 0.00 knockout mice proposed N/A
PV+ interneuron subtype diversification analysis exploratory neurodevelopmental disorders 0.750 0.00 mouse cortical PV+ interneuron proposed N/A
Cognitive Reserve Mechanisms in Alzheimer's Disease — Molecular Basis clinical Alzheimer's Disease 0.400 0.50 human proposed $6,550,000
Epigenetic Clocks in Neurodegeneration — Causal Drivers or Passive Mar validation Neurodegeneration 0.400 0.50 human proposed $3,000,000
Epigenetic Dysregulation Validation in Parkinson's Disease clinical Parkinson's Disease 0.400 0.50 human proposed $7,500,000
Lifestyle Intervention Mechanisms in Alzheimer's Disease validation Alzheimer's Disease 0.400 0.50 mouse proposed $430,000
Normal Aging to Alzheimer's Disease Transition Trigger — Identifying t validation Alzheimer's Disease 0.400 0.50 human proposed $2,280,000
Sirtuin Dysfunction Validation in Parkinson's Disease clinical Parkinson's Disease 0.400 0.50 human proposed $6,550,000
Sirtuin Pathway Dysfunction Validation in Parkinson's Disease clinical Parkinson's Disease 0.400 0.50 human proposed $6,550,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMIDAuthorsJournalYearCitations
NAD+ subcellular partitioning mediated by miR-183 and miR-96 regulates muscle st [PMID:41915008] Ma M, Ma R, Li Z, Shen S, Kong W, Qiu T, Journal of molecular cell biol 2026 0
Rhodiola sacra Protects Against Hippocampal Neuronal Apoptosis in Chronic Cerebr [PMID:41879438] Zhou L, Jia J, Li J, Yao Z, Fu Z, Wang S Current neuropharmacology 2026 0
Mechanistic Modulation of Autophagy by Bioactive Natural Products: Implications [PMID:41830033] Jalouli M, Harrath AH, Al-Zharani M, Rah Nutrients 2026 0
Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in [PMID:41645754] Li W, Wang WH, Song Y, Li XJ, Li Y et al Int J Mol Med 2026 0
Integrative SMR prioritizes oxidative stress-related regulatory genes for Alzhei [PMID:41844011] Wu L, Dong YT, Mu X, Luo X, Chen ZJ J Prev Alzheimers Dis 2026 0
Insulin resistance and SIRT1 dysregulation in neurodegenerative diseases. [PMID:41759326] Shah A, Doshi G Ageing research reviews 2026 0
Urolithin A Reverses Intranigral Rotenone-Generated Parkinsonism by Modulating D [PMID:41880654] Devi A, Singh SB, Srivastava S, Dandekar ACS chemical neuroscience 2026 0
Microglial Activation Under Hypoxic Conditions in Early Alzheimer's Disease: Can [PMID:41902653] Merlo S, Lipari CLR, Patti A, Sortino MA Phytotherapy research : PTR 2026 0
Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic net [PMID:41692938] Ungvari Z, Menyhárt O, Ocana A, Lehoczki GeroScience 2026 0
All the Way: A Decade of SIRT1 in Breast Cancer. [PMID:41898317] Pratelli G, Montalbano M, Affranchi F, O Biomedicines 2026 0
Therapeutic potential of sulforaphane in neurodegenerative diseases: mechanistic [PMID:41894075] Kuwar Omkar Kumar; Tejpal Sandip; Sharma Molecular biology reports 2026 0
Uncovering the metabolic-epigenetic links between gene expression and stroke: in [PMID:41877258] Kan J, Hong Y, Min R, Zhang B, Wang H Neurological research and prac 2026 0
Dysregulation of SIRT1, polyamines and miRNA editing in cancer and aging. [PMID:41863647] Ramamonjiharisoa MBM, Liu S Amino acids 2026 0
Immune-metabolic positive feedback model in COPD: cross-mechanisms and potential [PMID:41869013] Chen W, Huang S, He L, Zhou X, Li R, Wan Frontiers in cell and developm 2026 0
Unraveling Network Pharmacology-Based Therapeutics of Anthranilate Sulfonamides [PMID:41714304] Ruankham W, Prachayasittikul V, Pingaew Journal of neurochemistry 2026 0
Advances and Therapeutic Potential of Anthraquinone Compounds in Neurodegenerati [PMID:41868184] Liu Z, Zhang H, Wan B, Yin S, Yue R Drug design, development and t 2026 0
Integrative SMR prioritizes oxidative stress-related regulatory genes for Alzhei [PMID:41844011] Wu L, Dong YT, Mu X, Luo X, Chen ZJ The journal of prevention of A 2026 0
AMPK/SIRT1/PGC-1α Signaling Pathway: Molecular Mechanisms and Targeted Strategie [PMID:41268687] Chen J, Liu B, Yao X, Yang X, Sun J et a CNS Neurosci Ther 2025 0
Nicotinamide N-methyltransferase as a potential therapeutic target for neurodege [PMID:40221009] ["Liu A", "Zhu X", "Sun W", "Bi S", "Zha Experimental neurology 2025 0
PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Gl [PMID:39570804] Zhou Z, Yin X, Sun H, Lu J, Li Y, Fan Y, Cancer research 2025 0

Debates (16)

Multi-agent debates referencing this entity

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

closed · Rounds: 4 · Score: 0.81 · 2026-04-23

Investigate mechanisms of epigenetic reprogramming in aging neurons [TARGET_ART

closed · Rounds: 0 · Score: 0.50 · 2026-04-21

Investigate mechanisms of epigenetic reprogramming in aging neurons

closed · Rounds: 0 · Score: 0.56 · 2026-04-21

Investigate the therapeutic potential of clearing senescent cells (senolytics) t

closed · Rounds: 4 · Score: 0.75 · 2026-04-16

Epigenetic reprogramming in aging neurons

closed · Rounds: 4 · Score: 0.95 · 2026-04-10

Can circadian interventions reverse microglial priming independent of sleep disr

closed · Rounds: 4 · Score: 0.95 · 2026-04-10

Multiple NDDs converge on autophagy-lysosome dysfunction. Are there universal th

closed · Rounds: 4 · Score: 0.90 · 2026-04-06

Can speech, gait, retinal imaging, sleep, and smartphone data detect neurodegene

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP

closed · Rounds: 4 · Score: 0.89 · 2026-04-06

Sleep disruption as cause and consequence of neurodegeneration

closed · Rounds: 4 · Score: 0.91 · 2026-04-06