Genetic and molecular factors underlying human longevity and epigenetic aging

Area of Science:

• Genetics and Aging Research
• Molecular Biology
• Systems Biology

Background:

• Biological aging involves declining function and increased disease risk, with poorly understood factors and mechanisms.
• Epigenetic aging acceleration and human longevity are complex processes requiring further investigation.

Purpose of the Study:

• To identify risk factors and molecular phenotypes associated with epigenetic aging acceleration and human longevity.
• To elucidate the molecular mechanisms linking genetic variants to aging and longevity.
• To discover potential therapeutic targets for aging-related diseases.

Main Methods:

• Genome-wide association study (GWAS) was used to analyze aging-related traits and risk factors.
• Integration of GWAS data with multiple molecular quantitative trait loci (xQTL) datasets (eQTL, sQTL, apaQTL, pQTL, mQTL).
• Drug-target annotation using DrugBank to identify therapeutic candidates.

Main Results:

• Cholesterol levels, immune cell traits, and insulin-like growth factor-1 (IGF1) were associated with longevity.
• Identified 30 genes, 11 splicing events, 5 proteins, 3 alternative polyadenylation events, and 39 metabolites linked to aging.
• Prioritized CASP8, PSRC1, and SORT as potential therapeutic intervention targets.

Conclusions:

• This comprehensive analysis provides a resource for understanding the molecular basis of aging.
• Key regulatory mechanisms connecting genetic variants to epigenetic aging and longevity have been highlighted.
• Novel targets for precision interventions in aging-related diseases have been identified.