RT Journal Article T1 Epigenetic signatures, age acceleration, and injury risk in elite female and male soccer players A1 Fernández Pérez, Raúl A1 Lecumberri-Arteta, Jon A1 Kulis, Marta A1 Botta-Orfila, Teresa A1 Rodríguez-Vilarrupla, Aina A1 Yanguas, Xavier A1 Ferrer, Eva A1 Rodas, Gil A1 Martin-Subero, Jose I. AB 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 PB Nature Research YR 2025 FD 2025 LK https://hdl.handle.net/20.500.14352/128717 UL https://hdl.handle.net/20.500.14352/128717 LA eng NO Pérez, R. F., Lecumberri-Arteta, J., Kulis, M., Botta-Orfila, T., Rodríguez-Vilarrupla, A., Yanguas, X., Ferrer, E., Rodas, G., & Martin-Subero, J. I. (2025). Epigenetic signatures, age acceleration, and injury risk in elite female and male soccer players. Scientific reports, 15(1), 41826. https://doi.org/10.1038/s41598-025-25784-w NO Author contributionsG. Rodas and J.I. Martin-Subero designed and supervised the study; R.F. Pérez, J. Lecumberri-Arteta and M. Kulis extracted DNA and performed all the data analyses; T. Botta-Orfila and A. Rodriguez-Vilarrupla processed and stored samples; X. Yanguas, E. Ferrer and G. Rodas collected blood samples and injury parameters; R.F. Pérez, J. Lecumberri-Arteta, M. Kulis, G. Rodas and J.I. Martin-Subero wrote the manuscript with input from all other authors. DS Docta Complutense RD 21 mar 2026