Identification of age-accelerated organ signatures and aging-slowing signatures from exercise

Abstract

Aging drives cellular dysfunction and increases disease risk. However, effective biomarkers for personalized anti-aging interventions remain scarce. Exercise represents a effective intervention, but the molecular mechanisms underlying its slowing- or reverse-aging effects are incompletely understood. I performed SomaScan-based plasma proteomics in 19 participants (age 22-43) across three timepoints: pre-exercise, post-exercise, and 3-hour recovery, identifying exercise-responsive proteins (exerkines) using ANOVA and linear mixed models controlling for individual variability. I identified 35 robust exerkines exhibiting significant temporal dynamics with tissue mapping revealing multi-organ origins including blood, brain, liver, and muscle. Cross-validation using GTEx bulk RNA-seq data (17,382 samples) for aging associations and UK Biobank Olink proteomics (n=54,219) for muscle function correlations identified four proteins with compensatory reverse-aging patterns. ARL2BP emerged as the most robust candidate, showing decreased expression with aging but increased expression with exercise. This integrative multi-platform approach establishes a molecular framework linking exercise-responsive proteins to aging processes, providing circulating biomarkers for personalized anti-aging interventions and early identification of high-risk populations. MS/LS 20241021 Minseo Park (박민서). Identification of age-accelerated organ signatures and aging-slowing signatures from exercise (운동으로 인한 노화 촉진 및 노화 지연 장기 징후 식별). College of Life Science and Medical Engineering. Department of Life Sciences. 2026. 33p. Prof. Sunjae Lee