Epigenetic signatures, age acceleration, and injury risk in elite female and male soccer players

Physical activity has been extensively associated with epigenetic modifications. However, the potential contribution of DNA methylation patterns to sports injury susceptibility remains largely unexplored, particularly among high-performance athletes. Since methylation regulates genes involved in inflammation, tissue repair, and musculoskeletal function, altered methylation profiles may influence injury risk. Moreover, epigenetic clocks are increasingly used to assess vulnerability to clinical phenotypes, as accelerated epigenetic aging has been linked to various diseases. Here, we studied the DNA methylome of peripheral blood cells in 74 elite female and male soccer players with extensive non-contact injury follow-up. We aimed to explore alterations associated with increased injury risk and to describe the dynamics of epigenetic age acceleration in this group. Although DNA methylomes between players with higher and lower injury risk were overall similar, we identified 1081 differentially methylated CpGs sites that partly affected genes involved in skeletal muscle functions. We also estimated epigenetic age using eight clocks but found no association with injuries. However, male athletes displayed higher epigenetic age acceleration than females. Comparing the methylome of age-accelerated versus decelerated individuals revealed widespread changes across five clocks, strongly biased towards hypomethylation in age-accelerated players. Differential CpGs targeted genes enriched in extracellular matrix, cytoskeletal and collagen-related functions. Overall, this study suggests a link between DNA methylation and non-contact injuries in elite soccer players and shows that epigenetic age acceleration, although unrelated to injuries, is associated with widespread hypomethylation.