| Title: | From Genetic Susceptibility to Protein Pathways: Multi-omics Dissection of Lifestyle-Driven Biological Aging and Plasma Metabolites in Neurodegenerative Diseases: An Analysis Based on UK Biobank Data |
| Lead Institution: | The Third Affiliated Hospital Of Sun Yat-sen University |
| Principal investigator: |
Application 752659
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Research Question Can lifestyle factors (diet, exercise) interplay with genetic risks (APOE4, GBA) to disrupt protein homeostasis (neuroinflammation) and drive neurodegenerative diseases (NDDs) like Alzheimer's and Parkinson's via metabolic imbalances, accelerating biological aging? Core Hypothesis Genetic predisposition (polygenic risk scores) and protein dysregulation (GFAP, neurofilament light chain) mediate lifestyle-driven aging (epigenetic clocks, accelerometry) effects on NDD risk through systemic metabolite changes (ceramides, branched-chain amino acids). Objective Identify gene-protein-metabolite networks linking accelerated aging to NDDs. Assess lifestyle modulation (diet/exercise) of genetic risks on aging pathways. Validate protein biomarkers (e.g., complement proteins) bridging epigenetic aging, metabolites, and neurodegeneration phenotypes. Rationale NDD progression follows multi-omics interactions: Genetic susceptibility: Polygenic risk scores (PRS) integrate variants (e.g., CLU, PICALM) for baseline risk. Protein dysregulation: Plasma proteomics (Olink) detects neuronal damage (!NfL/GFAP) and inflammation (IL-6, TNF-!), linking aging to pathology. Metabolic dysfunction: Altered metabolites (!plasmalogens, !acyl-carnitines) reflect mitochondrial/membrane defects. Epigenetic clocks (e.g., DNAm GrimAge) connect lifestyle (e.g., smoking-associated methylation) to proteomic/metabolic shifts. The UK Biobank's multi-omics data (genomic, proteomic, metabolic, accelerometry) enables causal analysis across 500,000+ individuals.1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 20507 | NFAT3-high dysplastic clones drive IL-17C-mediated local epithelial remodeling and subtype-specific risk stratification in OPMDs | Yingxin Jiang (+6) | 2026 | ONCOLOGIE |
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