An epigenetic clock for chronological age estimation in East Asian populations

Abstract Background: The rapid rise in the older population over the past decade risks significant burden on healthcare, families, and society. This has drawn significant attention to aging research. DNA methylation is a heritable epigenetic alteration that is known to be linked with developmental processes via physiological and disease-associated changes. Hence, methylation changes are potential representatives of the natural aging process and age-related phenotypes, and are used as a predictor of chronological age. In this study, we explored the relationship between aging and changes in DNA methylation specifically among East-Asian (EAS) cohorts from Taiwan, Japan, and China to develop an epigenetic clock(definition). Methods : Following quality control, methylation data from EAS samples were used to develop a predictive model, east-Asian epigenetic clock (EAS clock). A stepwise multivariate regression model with forward-selection and Bayesian Information Criteria (BIC) was implemented to conduct variable selection. EAS clock’s performance was validated through rigorous statistical evaluation. Subgroup analyses across age intervals were conducted to assess age-specific efficacy. Additionally, functional enrichment analysis using Ingenuity Pathway Analysis (IPA) was performed to investigate the biological relevance of the selected CpG sites. Results : Correlation analysis between predicted and actual chronological age showed strong positive correlations in both training (r = 0.71, p < 0.0001) and testing (r = 0.68, p < 0.0001) sets. Difference between estimated age by the EAS clock and chronological age showed an approximate median and mean value of zero. Subgroup analysis implied that epigenetic aging may vary across the lifespan, especially at age extremes. Functional annotation revealed enrichment of CpG-associated genes in age-related pathways, including neurodegeneration, musculoskeletal disorders, and immune regulation. Compared with other methylation clocks, EAS clock demonstrated tighter residual clustering around zero, indicating improved accuracy. Conclusion : EAS clock, a robust and accurate epigenetic clock tailored to East Asian populations was developed. Early and precise epigenetic age prediction may support timely anti-aging interventions and disease management, potentially mitigating the individual and healthcare burden of aging.