Taiwan population-based epigenetic clocks and their application to long-term air pollution exposure

Area of Science:

• Epigenetics and Aging
• Environmental Epidemiology
• Population-Specific Biomarkers

Background:

• Existing epigenetic clocks are primarily developed in European/Hispanic cohorts, limiting their applicability to diverse populations.
• Population-specific epigenetic models are crucial for accurate assessment of biological aging and its determinants in Asian cohorts.
• Long-term air pollution exposure is a potential environmental factor influencing biological aging.

Purpose of the Study:

• To develop novel epigenetic clocks tailored for a Taiwanese population using Taiwan Biobank data.
• To investigate the association between long-term exposure to ambient air pollutants and epigenetic age acceleration (EAA).
• To assess the impact of PM2.5 and ozone on biological aging within an Asian cohort.

Main Methods:

• Developed Taiwanese epigenetic clocks (TWBAge, TWBhAge) using penalized elastic net regression on serum DNA methylation data from 2,469 participants.
• Estimated epigenetic age acceleration (EAA) metrics, including TWB-based (TWBEAA, TWBhEAA) and established clocks (DNAmEAA, DNAmSBEAA, PhenoEAA, GrimEAA).
• Assessed air pollution exposure (PM2.5, O3) using spatial interpolation and analyzed associations with EAA using multiple linear regression and Bayesian Kernel Machine Regression (BKMR).

Main Results:

• The developed TWBAge and TWBhAge models accurately predicted chronological age (R² = 0.95).
• Exposure to PM2.5 was significantly associated with increased TWBhEAA and DNAmEAA.
• Ozone (O3) exposure showed a positive association with DNAmSBEAA and a negative association with GrimEAA, confirmed by BKMR.

Conclusions:

• This study presents the first epigenetic clocks developed for an Asian population, demonstrating high predictive accuracy.
• Long-term exposure to PM2.5 and ozone significantly contributes to epigenetic age acceleration in the Taiwanese cohort.
• Findings underscore the importance of air pollution mitigation strategies for promoting healthy aging and reducing health disparities.