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.

3149Connections

20Hypotheses

30Analyses

50Outgoing

50Incoming

12Experiments

20Debates

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 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	SIRT1-Mediated Reversal of TREM2-Dependent Microgl Nutrient-Sensing Epigenetic Circuit Reactivation NRF2-Mediated Metabolic Reprogramming: HBOT as Dir (+6 more)
KG Connections	3148 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: SIRT1 — AlphaFold Q96EB6 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (8)

Knowledge base pages for this entity

Canonical Page

SIRT1 Gene

gene · 1038 words

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Validated Hypothesis: SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via PGC1alpha-Dependent GPX4 Upregulation in Post-CA Brain

hypothesis · 4606 words

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Validated Hypothesis: SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence

hypothesis · 4455 words

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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 (1760)

Target	Relation	Type	Str
SIRT1	encodes	protein	0.00
P53	activates	gene	1.00
INFLAMMATION	activates	gene	1.00
Cancer	activates	disease	1.00
GENES	activates	gene	1.00
autophagy	activates	process	1.00
MITOCHONDRIAL DYSFUNCTION	activates	gene	1.00
Neuroinflammation	activates	disease	1.00
Mitophagy	activates	pathway	1.00
Lipid Metabolism	activates	pathway	1.00
Neurodegeneration	activates	disease	1.00
Alzheimer	activates	disease	1.00
Inflammation	activates	disease	1.00
Obesity	activates	disease	1.00
AUTOPHAGY	activates	pathway	1.00
Inflammation	therapeutic_target	disease	1.00
INFLAMMATION	therapeutic_target	gene	1.00
Als	associated_with	disease	1.00
Mtor	activates	pathway	1.00
Autophagy	activates	pathway	1.00
Cardiac	activates	disease	1.00
Als	expressed_in	disease	1.00
Oxidative Stress	activates	pathway	1.00
Longevity	activates	disease	1.00
Tumor	activates	disease	1.00
Cancer	therapeutic_target	disease	1.00
Aging	activates	disease	1.00
NF-ΚB	activates	gene	1.00
AGING	activates	gene	1.00
Als	activates	disease	1.00
MTOR	activates	gene	1.00
Nf-Κb	activates	pathway	1.00
Senescence	activates	disease	1.00
Inflammation	regulates	disease	1.00
CANCER	activates	gene	1.00
Als	regulates	disease	1.00
ALZHEIMER	activates	gene	1.00
Parkinson	activates	disease	1.00
AMPK	activates	gene	1.00
Aging	regulates	disease	1.00
Apoptosis	activates	pathway	1.00
NEURODEGENERATIVE DISEASES	activates	gene	1.00
Oxidative Stress	therapeutic_target	pathway	1.00
PARKIN	activates	gene	1.00
Mitochondrial Function	activates	pathway	1.00
Apoptosis	therapeutic_target	pathway	1.00
Cardiovascular	therapeutic_target	disease	0.95
Senescence	therapeutic_target	disease	0.95
Histone Deacetylation	catalyzes	process	0.95
sarcopenia	regulates	disease	0.95

Incoming (1389)

Source	Relation	Type	Str
SIRT1	encodes	gene	0.00
ROS	activates	gene	1.00
NAD	associated_with	gene	1.00
INFLAMMATION	activates	gene	1.00
OXIDATIVE STRESS	activates	gene	1.00
NAD	regulates	gene	1.00
OXIDATIVE STRESS	therapeutic_target	gene	1.00
NAD	activates	gene	1.00
TNF	activates	gene	1.00
AMPK	activates	protein	0.98
NS5	interacts_with	protein	0.95
SRT2104	activates	drug	0.95
Melatonin	upregulates	drug	0.95
CHK1	interacts_with	protein	0.95
Srt2104	activates	drug	0.95
AMPK	associated_with	protein	0.95
Metformin	upregulates	drug	0.95
TBEV NS5	interacts_with	protein	0.93
h-827a821b	targets_gene	hypothesis	0.90
AUTOPHAGY	activates	gene	0.90
resveratrol	activates	drug	0.90
h-4bb7fd8c	targets	hypothesis	0.90
h-7c3c0f40	targets	hypothesis	0.90
NF-KB	associated_with	protein	0.90
Qigui Jiangzhi Formula	upregulates	drug	0.90
NMN	activates	drug	0.90
NAD+	activates	protein	0.90
h-c69709f5	targets	hypothesis	0.90
CHK1	phosphorylates	protein	0.90
h-var-b7de826706	targets_gene	hypothesis	0.90
NF-kB	inhibits	protein	0.90
NAD+	modulates	metabolite	0.90
Nmn	activates	drug	0.90
SIRT3	activates	gene	0.90
PINK1	activates	gene	0.90
APOPTOSIS	therapeutic_target	gene	0.90
PARKINSON'S DISEASE	activates	gene	0.90
SIRT3	expressed_in	gene	0.90
NAMPT	activates	protein	0.89
SMURF2	degrades	protein	0.88
NAMPT/NAD+ pathway	upstream_of	pathway	0.85
Oleic Acid	downregulates	compound	0.85
Resveratrol	activates	drug	0.85
intermittent fasting	activates	drug	0.85
Melatonin	activates	drug	0.85
NPFF	activates	protein	0.85
nicotinamide	targets	drug	0.85
time-restricted feeding	activates	process	0.85
tmTNF-α	upregulates	protein	0.85
NF-κB	interacts_with	pathway	0.85

Targeting Hypotheses (20)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc	0.893	neurodegeneration	Gene expression changes in aging mouse b
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt	0.824	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
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	Gut Microbiome Analysis in Parkinson's D
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
Nutrient-Sensing Epigenetic Circuit Reactivation	0.700	neurodegeneration	Epigenetic reprogramming in aging neuron
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
Caloric Restriction Mimetic Combination Therapy (Metformin +	0.640	neurodegeneration	-
NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/	0.602	neurodegeneration	What are the optimal oxygen pressure, du
NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Compl	0.592	neurodegeneration	test
SIRT1 Activation Suppresses C9orf72-Mediated Neurodegenerati	0.560	neurodegeneration	Test Preregistration Analysis
Astrocyte Metabolic Memory Reprogramming	0.541	neurodegeneration	How do astrocyte-neuron metabolic intera
SIRT1-Mediated Epigenetic Restoration of MFSD2A Expression R	0.500	neuropharmacology	What determines blood-brain barrier pene
SIRT1 Activator Therapy for Mitochondrial Epigenetic Dysregu	0.480	neurodegeneration	Comparative epigenetic signatures across
NAD+-SIRT1-H3K9me3 restoration enables true senescence rever	0.380	alzheimers	Can metabolic interventions truly revers
NAD+ Metabolic Rescue Via Autophagy-Epigenetic Coupling	0.000	-	Epigenetic clocks and biological aging i
Epigenetic Clock Reversal via Metabolic Oscillator Coupling	0.000	-	Epigenetic reprogramming in aging neuron
Metabolic-Epigenetic Coupling Interface (MECI)	0.000	-	Do different priming stimuli require dis

Mentioning Analyses (30)

Scientific analyses that reference this entity

Comparative epigenetic signatures: DNA methylation age acceleration and histone

neurodegeneration | 2026-04-18 | 0 hypotheses

Clinical Trial Landscaping for Alzheimer's Disease Therapeutics

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.629

Comparative epigenetic signatures across AD, PD, and ALS

neurodegeneration | 2026-04-16 | 7 hypotheses Top: 0.550

What molecular mechanisms cause iPLA2β deficiency to specifically damage mitocho

neurodegeneration | 2026-04-15 | 0 hypotheses

What are the specific circulating factors in exercise-conditioned plasma that me

neurodegeneration | 2026-04-14 | 2 hypotheses Top: 0.589

Experiments (12)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
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
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
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
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
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
Mechanistic Modulation of Autophagy by Bioactive Natural Products: Implications [PMID:41830033]	Jalouli M, Harrath AH, Al-Zharani M, Rah	Nutrients	2026
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
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
Insulin resistance and SIRT1 dysregulation in neurodegenerative diseases. [PMID:41759326]	Shah A, Doshi G	Ageing research reviews	2026
Urolithin A Reverses Intranigral Rotenone-Generated Parkinsonism by Modulating D [PMID:41880654]	Devi A, Singh SB, Srivastava S, Dandekar	ACS chemical neuroscience	2026
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
Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic net [PMID:41692938]	Ungvari Z, Menyhárt O, Ocana A, Lehoczki	GeroScience	2026
All the Way: A Decade of SIRT1 in Breast Cancer. [PMID:41898317]	Pratelli G, Montalbano M, Affranchi F, O	Biomedicines	2026
Therapeutic potential of sulforaphane in neurodegenerative diseases: mechanistic [PMID:41894075]	Kuwar Omkar Kumar; Tejpal Sandip; Sharma	Molecular biology reports	2026
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
Dysregulation of SIRT1, polyamines and miRNA editing in cancer and aging. [PMID:41863647]	Ramamonjiharisoa MBM, Liu S	Amino acids	2026
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
Unraveling Network Pharmacology-Based Therapeutics of Anthranilate Sulfonamides [PMID:41714304]	Ruankham W, Prachayasittikul V, Pingaew	Journal of neurochemistry	2026
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
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
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025
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
Nicotinamide N-methyltransferase as a potential therapeutic target for neurodege [PMID:40221009]	["Liu A", "Zhu X", "Sun W", "Bi S", "Zha	Experimental neurology	2025

Debates (20)

Multi-agent debates referencing this entity

Extended debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Debate: Chromatin Remodeling-Mediated Nutrient Sensing Restoration

closed · Rounds: 4 · Score: 0.46 · 2026-04-27

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 4 · Score: 0.44 · 2026-04-27

Hypothesis debate: Nutrient-Sensing Epigenetic Circuit Reactivation

closed · Rounds: 4 · Score: 0.46 · 2026-04-27

Hypothesis debate: SASP-Mediated Complement Cascade Amplification

closed · Rounds: 4 · Score: 0.40 · 2026-04-27

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

Epigenetic reprogramming of aging neurons represents an active research focus wi

closed · Rounds: 4 · Score: 0.67 · 2026-04-22

Related Research

Hypotheses and analyses mentioning SIRT1 in their description or question text

SIRT1

Understanding Entity Pages

Summary

Wiki Pages (8)

SIRT1 Gene

Validated Hypothesis: SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via PGC1alpha-Dependent GPX4 Upregulation in Post-CA Brain

Validated Hypothesis: SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence

Epigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor

SIRT1 Signaling Pathway in Alzheimer's Disease

SIRT1 Activators for Parkinson's Disease

SIRT1 Protein

SIRT1 (Redirect)

Pathway Diagram

Outgoing (1760)

Incoming (1389)

Targeting Hypotheses (20)

Mentioning Analyses (30)

Comparative epigenetic signatures: DNA methylation age acceleration and histone

Clinical Trial Landscaping for Alzheimer's Disease Therapeutics

Comparative epigenetic signatures across AD, PD, and ALS

What molecular mechanisms cause iPLA2β deficiency to specifically damage mitocho

What are the specific circulating factors in exercise-conditioned plasma that me

What specific gene expression signatures in aging mouse brain predict human AD v

Which specific post-translational modifications create druggable epitopes unique

Can circadian interventions selectively target microglia without affecting other

Investigate mechanisms of epigenetic reprogramming in aging neurons

Do different priming stimuli require distinct therapeutic approaches or share co

Can circadian interventions reverse microglial priming independent of sleep disr

What specific astrocyte-derived factors can 'erase' pathological microglial memo

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

Investigate mechanisms of epigenetic reprogramming in aging neurons

Epigenetic reprogramming in aging neurons

epigenetic reprogramming aging neurons

Senescent cell clearance as neurodegeneration therapy

Which metabolic biomarkers can distinguish therapeutic response from disease pro

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

How do astrocyte-neuron metabolic interactions change during disease progression

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

CRISPR-based therapeutic approaches for neurodegenerative diseases

Epigenetic reprogramming in aging neurons

Senescent cell clearance as neurodegeneration therapy

CRISPR-based therapeutic approaches for neurodegenerative diseases

Epigenetic clocks and biological aging in neurodegeneration

Sleep disruption as cause and consequence of neurodegeneration

Digital biomarkers and AI-driven early detection of neurodegeneration

Senolytic therapy for age-related neurodegeneration

Autophagy-lysosome pathway convergence across neurodegenerative diseases

Experiments (12)

Related Papers (20)

Debates (20)

Extended debate: Metabolic Reprogramming to Reverse Senescence

Debate: Chromatin Remodeling-Mediated Nutrient Sensing Restoration

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

Hypothesis debate: Nutrient-Sensing Epigenetic Circuit Reactivation

Hypothesis debate: SASP-Mediated Complement Cascade Amplification

Hypothesis debate: SASP Modulation Rather Than Cell Elimination

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

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

Epigenetic reprogramming of aging neurons represents an active research focus wi

Related Research

TREM2-SIRT1 Metabolic Senescence Circuit in Microglial Aging

Nutrient-Sensing Epigenetic Circuit Reactivation

NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogramming Toward Senescen

LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation via SIRT1/PGC1α Sup

NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/SIRT1 Activator for

NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement Amplification

SIRT1 Activation Suppresses C9orf72-Mediated Neurodegeneration

Astrocyte Metabolic Memory Reprogramming

SIRT1-Mediated Epigenetic Restoration of MFSD2A Expression Re-enables SPM Precur

SIRT1 Activator Therapy for Mitochondrial Epigenetic Dysregulation

NAD+-SIRT1-H3K9me3 restoration enables true senescence reversal, while incomplet

NAD+ Metabolic Rescue Via Autophagy-Epigenetic Coupling

Epigenetic Clock Reversal via Metabolic Oscillator Coupling

Metabolic-Epigenetic Coupling Interface (MECI)