SIRT1 Activator Therapy for Mitochondrial Epigenetic Dysregulation
Curated pathway from expert analysis
flowchart TD
A["NAD+ Availability<br/>NAMPT-Dependent"]
B["SIRT1 Activation<br/>NAD+-Dependent Deacetylase"]
C["PGC1alpha Deacetylation<br/>Mitochondrial Gene Activation"]
D["Mitochondrial Biogenesis<br/>Oxidative Phosphorylation"]
E["FOXO Deacetylation<br/>Antioxidant Response"]
F["NF-kB p65 Deacetylation<br/>Inflammation Suppression"]
G["Tau Deacetylation<br/>Proteasomal Clearance"]
H["Neuroprotection<br/>Extended Lifespan"]
A --> B
B --> C
B --> E
B --> F
B --> G
C --> D
D --> H
E --> H
F --> H
G --> H
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for SIRT1 pathway / NAD+ metabolism from GTEx v10.
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for SIRT1 pathway.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF C. elegans expressing human α-synuclein are treated with SRT2104 (10 mg/kg daily) for 14 days THEN mitochondrial network integrity scores will increase by ≥25% relative to vehicle controls. | Mitochondrial network integrity score (assessed via TOM20 staining and automated morphometric analysis) will increase by ≥25% in SRT2104-treated animals compare | — no observation — | pending | 0.55 |
| IF aged C57BL/6J mice receive nicotinamide riboside supplementation (400 mg/kg/day) in combination with voluntary exercise for 8 weeks THEN brain NAD+ concentrations will increase by ≥50% and cortical | Brain NAD+ concentrations will increase by ≥50% and mitochondrial DNA copy number will increase by ≥30% in the combination therapy group | — no observation — | pending | 0.50 |