Epigenetic Aging as a Predictor of Immune Decline Across the Human Lifespan

Biological aging varies considerably between individuals of the same chronological age, reflecting differences in molecular and cellular processes that accumulate over time. DNA methylation patterns have emerged as one of the strongest biomarkers of biological age, giving rise to epigenetic clocks that estimate an individual's biological rather than chronological age. While accelerated epigenetic aging has been associated with increased mortality and age-related disease, its relationship with the gradual deterioration of immune function remains incompletely understood. Most studies examine aging and immunity independently, leaving unanswered whether molecular indicators of biological age consistently predict declines in immune competence across diverse populations. This project investigates whether epigenetic age acceleration is associated with measurable changes in immune system composition and function using large population-based cohorts containing paired DNA methylation profiles and immunological measurements. Biological age will be estimated using established epigenetic clocks, while immune phenotypes will include circulating leukocyte populations, inflammatory cytokine levels, lymphocyte subsets, and markers of immune activation. Statistical models will evaluate whether individuals whose biological age exceeds their chronological age exhibit signatures of accelerated immunosenescence after controlling for demographic, clinical, and lifestyle variables. The central question is whether epigenetic aging provides predictive information about immune decline beyond chronological age alone. The group will analyze publicly available longitudinal cohorts containing genome-wide DNA methylation and immune profiling data, comparing multiple epigenetic clock models to determine which most accurately predicts age-related immune dysfunction. Regression analyses, survival modeling, and feature importance methods will quantify associations between biological age acceleration and individual immune biomarkers while assessing consistency across independent cohorts.