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.
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.
AI-generated illustration
Regenerate portrait ↻| Gene Symbol | SIRT1 |
| Chromosome | 10q21.3<br> |
| Target Class | Epigenetic Regulator |
| Function | SIRT1 uses NAD+ as a cofactor, linking its activity to cellular energy status and metabolic health. |
| Mechanism of Action | SIRT1 activation via NAD+ precursors or allosteric activators deacetylates tau (reducing aggregation), enhances mitophagy, and restores circadian gene expression |
| Druggability | Medium (0.48) |
| Clinical Stage | Phase III |
| Pathways | Akt, Ampk Signaling, Angiogenesis, Apoptosis, Autophagy |
| UniProt ID | Q96EB6 |
| NCBI Gene ID | 23411 |
| Ensembl ID | ENSG00000096717 |
| GeneCards | SIRT1 |
| Human Protein Atlas | SIRT1 |
| Associated Diseases | aging, aging-related diseases, Als, Alzheimer |
| Known Drugs/Compounds | curcumin, DSS, EDARAVONE, Ginsenoside Re, intermittent fasting, kaempferol |
| Interactions | ABCA1, ACAT1, ACETYL-COA, ACHE, ACOX1, ACTB |
| SciDEX Target | View Target Profile (6 clinical trials) |
| SciDEX Hypotheses | Nutrient-Sensing Epigenetic Circuit Reactivation SIRT1-Mediated Reversal of TREM2-Dependent Microgl NRF2-Mediated Metabolic Reprogramming: HBOT as Dir (+2 more) |
| KG Connections | 3063 knowledge graph edges |
| Databases | GeneCardsHPASTRING |
🔮 Predicted Structure: SIRT1 — AlphaFold Q96EB6 Click to expand
Wiki Pages (6)
Knowledge base pages for this entity
SIRT1 Gene
gene · 1038 wordsEpigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor
idea · 3877 wordsSIRT1 Signaling Pathway in Alzheimer's Disease
pathway · 2490 wordsSIRT1 Activators for Parkinson's Disease
mechanism · 1622 wordsSIRT1 Protein
protein · 1592 wordsSIRT1 (Redirect)
redirect · 593 wordsPathway 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:#e0e0e0Outgoing (1684)
| Target | Relation | Type | Str |
|---|---|---|---|
| SIRT1 | encodes | protein | 0.00 |
| NF-ΚB | activates | gene | 1.00 |
| Tumor | activates | disease | 1.00 |
| Oxidative Stress | activates | pathway | 1.00 |
| Mtor | activates | pathway | 1.00 |
| Als | associated_with | disease | 1.00 |
| INFLAMMATION | therapeutic_target | gene | 1.00 |
| ALZHEIMER | activates | gene | 1.00 |
| Inflammation | therapeutic_target | disease | 1.00 |
| Alzheimer | activates | disease | 1.00 |
| Nf-Κb | activates | pathway | 1.00 |
| Mitophagy | activates | pathway | 1.00 |
| Apoptosis | activates | pathway | 1.00 |
| P53 | activates | gene | 1.00 |
| Parkinson | activates | disease | 1.00 |
| Inflammation | activates | disease | 1.00 |
| Inflammation | regulates | disease | 1.00 |
| Aging | regulates | disease | 1.00 |
| autophagy | activates | process | 1.00 |
| Lipid Metabolism | activates | pathway | 1.00 |
| INFLAMMATION | activates | gene | 1.00 |
| Als | regulates | disease | 1.00 |
| Aging | activates | disease | 1.00 |
| Als | activates | disease | 1.00 |
| Longevity | activates | disease | 1.00 |
| Neurodegeneration | activates | disease | 1.00 |
| MTOR | activates | gene | 1.00 |
| MITOCHONDRIAL DYSFUNCTION | activates | gene | 1.00 |
| AMPK | activates | gene | 1.00 |
| CANCER | activates | gene | 1.00 |
| Cancer | therapeutic_target | disease | 1.00 |
| AGING | activates | gene | 1.00 |
| Obesity | activates | disease | 1.00 |
| GENES | activates | gene | 1.00 |
| Als | expressed_in | disease | 1.00 |
| Cancer | activates | disease | 1.00 |
| Cardiac | activates | disease | 1.00 |
| Neuroinflammation | activates | disease | 1.00 |
| Senescence | activates | disease | 1.00 |
| AUTOPHAGY | activates | pathway | 1.00 |
| Autophagy | activates | pathway | 1.00 |
| PARKIN | activates | gene | 1.00 |
| Apoptosis | therapeutic_target | pathway | 1.00 |
| Oxidative Stress | therapeutic_target | pathway | 1.00 |
| Mitochondrial Function | activates | pathway | 1.00 |
| NEURODEGENERATIVE DISEASES | activates | gene | 1.00 |
| MAFLD | regulates | disease | 0.95 |
| Diabetes | activates | disease | 0.95 |
| Histone Deacetylation | catalyzes | process | 0.95 |
| Inflammation | associated_with | disease | 0.95 |
Incoming (1380)
| Source | Relation | Type | Str |
|---|---|---|---|
| SIRT1 | encodes | gene | 0.00 |
| NAD | associated_with | gene | 1.00 |
| NAD | regulates | gene | 1.00 |
| OXIDATIVE STRESS | activates | gene | 1.00 |
| INFLAMMATION | activates | gene | 1.00 |
| ROS | activates | gene | 1.00 |
| NAD | activates | gene | 1.00 |
| OXIDATIVE STRESS | therapeutic_target | gene | 1.00 |
| TNF | activates | gene | 1.00 |
| AMPK | activates | protein | 0.98 |
| Melatonin | upregulates | drug | 0.95 |
| Srt2104 | activates | drug | 0.95 |
| CHK1 | interacts_with | protein | 0.95 |
| AMPK | associated_with | protein | 0.95 |
| Metformin | upregulates | drug | 0.95 |
| SRT2104 | activates | drug | 0.95 |
| NS5 | interacts_with | protein | 0.95 |
| TBEV NS5 | interacts_with | protein | 0.93 |
| Qigui Jiangzhi Formula | upregulates | drug | 0.90 |
| NAD+ | modulates | metabolite | 0.90 |
| AUTOPHAGY | activates | gene | 0.90 |
| h-7c3c0f40 | targets | hypothesis | 0.90 |
| h-var-b7de826706 | targets_gene | hypothesis | 0.90 |
| h-827a821b | targets_gene | hypothesis | 0.90 |
| h-c69709f5 | targets | hypothesis | 0.90 |
| h-4bb7fd8c | targets | hypothesis | 0.90 |
| NAD+ | activates | protein | 0.90 |
| CHK1 | phosphorylates | protein | 0.90 |
| NF-kB | inhibits | protein | 0.90 |
| resveratrol | activates | drug | 0.90 |
| NF-KB | associated_with | protein | 0.90 |
| SIRT3 | activates | gene | 0.90 |
| SIRT3 | expressed_in | gene | 0.90 |
| PARKINSON'S DISEASE | activates | gene | 0.90 |
| PINK1 | activates | gene | 0.90 |
| APOPTOSIS | therapeutic_target | gene | 0.90 |
| NAMPT | activates | protein | 0.89 |
| SMURF2 | degrades | protein | 0.88 |
| NPFF | activates | protein | 0.85 |
| nicotinamide | targets | drug | 0.85 |
| Oleic Acid | downregulates | compound | 0.85 |
| Resveratrol | activates | drug | 0.85 |
| tmTNF-α | upregulates | protein | 0.85 |
| intermittent fasting | activates | drug | 0.85 |
| time-restricted feeding | activates | process | 0.85 |
| Melatonin | activates | drug | 0.85 |
| NF-κB | interacts_with | pathway | 0.85 |
| NAMPT/NAD+ pathway | upstream_of | pathway | 0.85 |
| APOPTOSIS | associated_with | gene | 0.82 |
| ALZHEIMER'S DISEASE | associated_with | disease | 0.82 |
Targeting Hypotheses (15)
Hypotheses where this entity is a therapeutic target
Mentioning Analyses (13)
Scientific analyses that reference this entity
Comparative epigenetic signatures across AD, PD, and ALS
neurodegeneration | 2026-04-16 | 7 hypotheses Top: 0.550
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: 0.937
Senescent cell clearance as neurodegeneration therapy
neurodegeneration | 2026-04-04 | 7 hypotheses Top: 1.000
Experiments (12)
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. 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 |
| Epigenetic clocks association with brain aging patterns in older women | exploratory | cognitive impairment and demen | 0.900 | 0.00 | human patients | 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 | completed | $6,550,000 |
| Epigenetic Clocks in Neurodegeneration — Causal Drivers or Passive Mar | validation | Neurodegeneration | 0.400 | 0.50 | human | completed | $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 & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| 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 |
| Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] | ["Chen Kai", "Li Fuyao", "Zhang Shuwen", | Journal of neuroinflammation | 2025 | 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 |
Debates (19)
Multi-agent debates referencing this entity
Hypothesis debate: SASP Modulation Rather Than Cell Elimination
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: Metabolic Reprogramming to Reverse Senescence
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
Hypothesis debate: Metabolic Reprogramming to Reverse Senescence
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
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
What are the shared DNA methylation age acceleration and histone modification pa
closed · Rounds: 4 · Score: 0.50 · 2026-04-18
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
Related Research
Hypotheses and analyses mentioning SIRT1 in their description or question text
H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from Epigenomic Homeostasi
Score: 0.770 · neurodegeneration · 2026-04-22
## Mechanistic Overview H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from Epigenomic Homeostasis starts from th
TREM2-SIRT1 Metabolic Senescence Circuit in Microglial Aging
Score: 0.744 · neurodegeneration · 2026-04-12
**Molecular Mechanism and Rationale** The TREM2-SIRT1 metabolic senescence circuit represents a critical regulatory net
NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogramming Toward Senescen
Score: 0.700 · neurodegeneration · 2026-04-22
## **Molecular Mechanism and Rationale** The molecular foundation of this hypothesis centers on the intricate relations
LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation via SIRT1/PGC1α Sup
Score: 0.666 · neurodegeneration · 2026-04-16
## Mechanistic Overview LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation via SIRT1/PGC1α Suppression starts
NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/SIRT1 Activator for
Score: 0.602 · neurodegeneration · 2026-04-17
## Mechanistic Overview NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/SIRT1 Activator for Reverse Senescen
NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement Amplification
Score: 0.592 · neurodegeneration · 2026-04-16
## Mechanistic Overview NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement Amplification starts from the
Astrocyte Metabolic Memory Reprogramming
Score: 0.541 · neurodegeneration · 2026-04-12
## Mechanistic Overview Astrocyte Metabolic Memory Reprogramming starts from the claim that modulating SIRT1 within the
SIRT1-Mediated Epigenetic Restoration of MFSD2A Expression Re-enables SPM Precur
Score: 0.498 · neuropharmacology · 2026-04-13
## Mechanistic Overview SIRT1-Mediated Epigenetic Restoration of MFSD2A Expression Re-enables SPM Precursor Transport in
SIRT1 Activator Therapy for Mitochondrial Epigenetic Dysregulation
Score: 0.480 · neurodegeneration · 2026-04-25
SIRT1 Activator Therapy for Mitochondrial Epigenetic Dysregulation
NAD+-SIRT1-H3K9me3 restoration enables true senescence reversal, while incomplet
Score: 0.000 · Alzheimer's disease · 2026-04-26
Partial metabolic interventions (e.g., mTOR inhibition alone) suppress SASP secretion but leave growth arrest intact bec