concept

AGE

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about AGE: 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.

43Connections

30Hypotheses

1Analyses

24Outgoing

19Incoming

2Experiments

1Debates

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💡 Concept Info

Name	AGE
Key Genes/Proteins	AGER
Related Diseases	AD, ALS, neurodegenerative diseases, PD
Linked Hypotheses	3 hypotheses

Wiki Pages (9)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    AGE["AGE"]
    AGE -->|"risk_factor_for"| Alzheimer_s_Disease["Alzheimer's Disease"]
    AGE -->|"risk_factor_for"| Parkinson_s_Disease["Parkinson's Disease"]
    AGE -->|"risk_factor_for"| Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
    AGE -->|"downregulates"| Microglial_Phagocytosis_of_Amy["Microglial Phagocytosis of Amyloid-beta"]
    AGE -->|"upregulates"| Microglial_Phagocytosis_of_Syn["Microglial Phagocytosis of Synapses"]
    AGE -->|"risk_factor_for"| Glaucoma["Glaucoma"]
    AGE -->|"modulates"| Mature_Neuronal_Fate["Mature Neuronal Fate"]
    AGE -->|"risk_factor_for"| Dementia["Dementia"]
    PARKINSON["PARKINSON"] -->|"increases_risk"| AGE
    autophagy["autophagy"] -->|"regulates"| AGE

Outgoing (24)

Target	Relation	Type	Str
Alzheimer's Disease	risk_factor_for	disease	0.95
Dopaminergic Neurodegeneration	associated_with	process	0.95
Neuronal Fate Instability	associated_with	phenotype	0.95
Parkinson's Disease	risk_factor_for	disease	0.90
Amyotrophic Lateral Sclerosis	risk_factor_for	disease	0.90
Microglial Phagocytosis of Amyloid-β	downregulates	process	0.90
Microglial Phagocytosis of Synapses	upregulates	process	0.90
Strem2	upregulates	protein	0.88
Mature Neuronal Fate	modulates	phenotype	0.85
Trem2 Processing	modulates	process	0.85
Glaucoma	risk_factor_for	disease	0.85
microglia-peripheral macrophage differentiation	regulates	process	0.85
Dementia	risk_factor_for	disease	0.82
neurodegenerative diseases	risk_factor	disease	0.80
microglial heterogeneity	drives	phenotype	0.80
Hyperphosphorylated Tau Accumulation	associated_with	process	0.80
Microglial Population Differences	associated_with	phenotype	0.80
Dementia Development	associated_with	phenotype	0.80
Trem2 Function	modulates	mechanism	0.78
Alzheimer's disease	associated_with	disease	0.70
terminally inflammatory microglia	activates	cell_type	0.70
ALS	associated_with	disease	0.64
AD	associated_with	disease	0.64
PD	associated_with	disease	0.64

Incoming (19)

Source	Relation	Type	Str
35361905	breaks down with	paper	0.90
25611508	correlates with	paper	0.90
26175670	declined with	paper	0.90
33132847	increases	paper	0.90
41224757	is associated with delay in	paper	0.90
41254697	is the primary risk factor for	paper	0.90
41224757	causes delay in	paper	0.90
40991070	correlates with	paper	0.90
41495755	enhances	paper	0.90
41495755	causes	paper	0.90
Microglia Phenotype	associated_with	phenotype	0.85
PARKINSON	increases_risk	disease	0.80
Asc Clusters Density	correlates_with	biomarker	0.80
autophagy	regulates	pathway	0.70
35035879	correlates negatively with	paper	0.60
35035879	correlate negatively with	paper	0.60
41495755	influences	paper	0.60
AGER	co_associated_with	gene	0.30
Bd-Tau	correlates_with	biomarker	0.30

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microgli	0.921	neurodegeneration	TREM2 in Alzheimer's Disease: Mechanisms
Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Pa	0.887	-	Do β-amyloid plaques and neurofibrillary
Focused Ultrasound with Microbubble Contrast Agents for Anti	0.886	neurodegeneration	Blood-brain barrier antibody transport m
TYROBP (DAP12) Conditional Antagonism for Early-Stage Neurop	0.844	neurodegeneration	TREM2 agonism vs antagonism in DAM micro
Elevated CSF/Serum Albumin Quotient Predicts Neurodegenerati	0.825	-	What blood-brain barrier permeability ch

TBK1 Loss Locks Microglia in an Aged/Senescent Transcription	0.776	ALS	What are the mechanisms by which microgl
age-linked CpG drift is the actionable driver in: Are DNA me	0.750	neurodegeneration	Are DNA methylation changes in neurodege
age-linked CpG drift is the actionable driver in: Are age-re	0.750	neurodegeneration	Are age-related DNA methylation changes
Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT Ove	0.745	neurodegeneration	Epigenetic reprogramming in aging neuron
VPS35 retromer activation prevents endosomal tau templating	0.740	neurodegeneration	Which tau propagation mechanism predomin
Mutant-dependent amplification is context-dependent and stro	0.740	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
ATAC-seq accessibility separates causal from compensatory st	0.738	neurodegeneration	Are age-related DNA methylation changes
Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in	0.735	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro
Context-Dependent Cx43 Modulation Based on Disease Stage	0.724	cell biology	What is the relative contribution of con
protective chromatin remodeling defines the therapeutic wind	0.723	neurodegeneration	Are age-related DNA methylation changes
Peripheral Monocyte/Macrophage Infiltration Mimicking Microg	0.693	neuroinflammation	What causes IBA1 low/negative microglia
PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Su	0.661	neurodegeneration	What upstream mechanisms trigger p53 act
Focused Ultrasound with Microbubble Contrast Agents	0.660	drug delivery	Can IGFBPL1 therapeutics effectively cro
Plasma D-Dimer Elevation Reflects Fibrinogen Leakage and Sec	0.660	-	What blood-brain barrier permeability ch
Radiation drives pericyte senescence through lysosome acidif	0.652	neurodegeneration	What specific autophagy pathways are def
Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia C	0.649	neurodegeneration	Gene expression changes in aging mouse b
IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral	0.648	neuroinflammation	How do B cells mechanistically orchestra
S100B as Active Pathogenic BBB-Disrupting Signal via RAGE/NF	0.647	-	Blood-brain barrier permeability changes
C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque Macropha	0.640	neuroinflammation	What are the specific molecular mechanis
Mitochondrial ROS from complex I and cardiolipin instability	0.640	neurodegeneration	What mechanisms drive the self-amplifyin
HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf	0.640	neurodegeneration	What are the optimal oxygen pressure, du
Age-Stratified Dosing Protocol Reflecting Endogenous Decline	0.640	-	What is the optimal dosage and timing of
Mitochondrial NAD+ Salvage Enhancement	0.639	neurodegeneration	Gene expression changes in aging mouse b
Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in	0.637	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro
TREM2 Antagonism in Late-Stage Tauopathy — Reducing Neuroinf	0.628	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro

Mentioning Analyses (1)

Scientific analyses that reference this entity

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

neurodegeneration | 2026-04-01 | 13 hypotheses Top: 0.888

Experiments (2)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Epigenetic clocks association with brain aging patterns in older women	exploratory	cognitive impairment and demen	0.900	0.00	human patients	proposed	N/A
Conditional TYROBP Knockdown in Early-Stage 5xFAD Mice Using CRISPRi-A	in_vivo	Alzheimer's disease	0.746	0.55	5xFAD x Cx3cr1-Cre mice inject	proposed	$95,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS [PMID:33031745]	Yu CH, Davidson S, Harapas CR, Hilton JB	Cell	2020	2
Genome-wide methylation profiles reveal quantitative views of human aging rates. [PMID:23177740]	Hannum G, Guinney J, Zhao L, Zhang L, Hu	Mol Cell	2013	1
Genome-wide consensus transcriptional signatures identify synaptic pruning linki [PMID:41139712]	Li H, Xie Z, Tian Y, Zhou R, Yang Y et a	Mol Psychiatry	2026	0
The Alzheimer's disease risk genes MS4A4A and MS4A6A cooperate to negatively reg [PMID:41435829]	Rosner D, Sun J, Cacace R, Yee A, Wagh C	Neuron	2026	0
Extracellular vesicles from IPFP-MSCs trigger osteoarthritis by transferring mtD [PMID:41480405]	Li S, Yan Z, Zhi X, Zheng W, Zhang Z et	Bioact Mater	2026	0
Integrative Transcriptomic and Bioinformatics Approaches Combined With Transform [PMID:41524613]	Yan D, Li W, Xing E, Wang P, Zhang Z	FASEB J	2026	0
Comprehensive multi-omics analysis and experimental validation indicate that VPS [PMID:41531939]	Wan D, Qi Y, Kang Y, Liang F, Wang Q et	RSC Med Chem	2026	0
Integrated Bioinformatics Analysis of Screen Mitochondrial Autophagy-Related Cor [PMID:41731906]	Gao Z, Wang Y, Ren Y, Lyu J	J Neurochem	2026	0
VPS35 Deficiency Markedly Reduces the Proliferation of HEK293 Cells. [PMID:41751560]	Lee S, Park S, Bang H, Kim SU, Park YH e	Genes (Basel)	2026	0
N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in P [PMID:41766663]	Song P, Chen C, Franchini R, Duong B, Wa	J Clin Invest	2026	0
The VPS35 protein and the role of its impairments in mitochondrial dysfunction i [PMID:41841708]	Buneeva OA, Medvedev AE	Biomed Khim	2026	0
Vps35 p. D620N causes Lrrk2 kinase hyperactivity, chronic microglial activation [PMID:41846978]	Deng IB, Bu M, Follett J, Sharp R, Mamai	bioRxiv	2026	0
Lack of Cerebrospinal Fluid α-Synuclein Seeding in VPS35 D620N- and LRRK2 Y1699C [PMID:41912440]	Santinelli L, Pratuseviciute N, Lange LM	Mov Disord	2026	0
Integrative bioinformatics and machine learning identify shared molecular mechan [PMID:41961800]	Deng A, Wang W	PLoS One	2026	0
Genome-wide consensus transcriptional signatures identify synaptic pruning linki [PMID:41139712]	Li H, Xie Z, Tian Y, Zhou R, Yang Y, Lin	Molecular psychiatry	2026	0
The Alzheimer's disease risk genes MS4A4A and MS4A6A cooperate to negatively reg [PMID:41435829]	Rosner D, Sun J, Cacace R, Yee A, Wagh C	Neuron	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
DNA methylation and prediction of biological age. [PMID:41602542]	Chen Y, Cheng X, Ji S	Front Mol Biosci	2025	0
The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkins [PMID:39964974]	Dai L, Wang J, Meng L, Zhang X, Xiao T,	PLoS biology	2025	0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0

Debates (1)

Multi-agent debates referencing this entity

What are the mechanisms underlying what are the mechanisms by which gut microbio

closed · Rounds: 4 · Score: 0.95 · 2026-04-01

Related Research

Hypotheses and analyses mentioning AGE in their description or question text

TBK1 Loss Locks Microglia in an Aged/Senescent Transcriptional State, Fueling AL

Score: 0.776 · ALS · 2026-04-26

age-linked CpG drift is the actionable driver in: Are DNA methylation changes in

Score: 0.750 · neurodegeneration · 2026-04-26

The gap can be tested by treating age-linked CpG drift as an upstream driver rather than a passive correlate. If true, p

age-linked CpG drift is the actionable driver in: Are age-related DNA methylatio

Score: 0.750 · neurodegeneration · 2026-04-26

The gap can be tested by treating age-linked CpG drift as an upstream driver rather than a passive correlate. If true, p

Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT Overexpression

Score: 0.745 · neurodegeneration · 2026-04-12

**Molecular Mechanism and Rationale** The NAD+ salvage pathway represents a critical metabolic hub in neuronal energy h

VPS35 retromer activation prevents endosomal tau templating across all brain reg

Score: 0.740 · neurodegeneration · 2026-04-21

## Mechanistic Overview VPS35 retromer activation prevents endosomal tau templating across all brain regions and disease

Mutant-dependent amplification is context-dependent and strongest in microglia a

Score: 0.740 · neurodegeneration · 2026-04-24

A credible refinement is that any true amplification is not universal across cell types, but emerges most strongly in pr

ATAC-seq accessibility separates causal from compensatory states in: Are age-rel

Score: 0.738 · neurodegeneration · 2026-04-26

A longitudinal biomarker panel centered on ATAC-seq accessibility can distinguish harmful mechanisms from protective ada

Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in Amyloid Phase, Anta

Score: 0.735 · Alzheimer's disease · 2026-04-04

## Mechanistic Overview Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in Amyloid Phase, Antagonist in Tau Ph

Context-Dependent Cx43 Modulation Based on Disease Stage

Score: 0.724 · cell biology · 2026-04-13

## Mechanistic Overview Context-Dependent Cx43 Modulation Based on Disease Stage starts from the claim that modulating G

protective chromatin remodeling defines the therapeutic window for: Are age-rela

Score: 0.723 · neurodegeneration · 2026-04-26

The same signal may be beneficial early and damaging late. Testing protective chromatin remodeling with single-cell meth

Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial Loss

Score: 0.693 · neuroinflammation · 2026-04-21

**Molecular Mechanism and Rationale** The proposed mechanism centers on liver disease-induced breakdown of blood-brain

PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 Activat

Score: 0.661 · neurodegeneration · 2026-04-15

## Mechanistic Overview PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 Activation starts from

Focused Ultrasound with Microbubble Contrast Agents

Score: 0.660 · drug delivery · 2026-04-22

## **Molecular Mechanism and Rationale** The molecular foundation of focused ultrasound (FUS) with microbubble contrast

Plasma D-Dimer Elevation Reflects Fibrinogen Leakage and Secondary Fibrinolysis

Score: 0.660 · unknown disease · 2026-04-26

Plasma fibrinogen leaks across the compromised BBB and undergoes coagulation cascade activation and cross-linking by fac

Radiation drives pericyte senescence through lysosome acidification failure and

Score: 0.652 · neurodegeneration · 2026-04-25

Autophagosomes still form after irradiation, but damaged lysosomes cannot clear cargo, sustaining ROS and SASP output.

AGE