Acute capillary blood DNA methylation responses to swimming exercise in high-performance male and female swimmers

Epigenetic markers, particularly DNA methylation, are promising tools for monitoring athlete health and training due to their role in cellular regulation, exercise responsiveness and molecular stability. However, exercise-induced epigenetic changes in peripheral blood in trained individuals remain unexplored. Therefore, we investigated the whole blood DNA methylation responses to swimming performed in the moderate (below critical speed) and severe (above critical speed) intensity domains using minimally invasive sampling. Ten high-performance swimmers (5 males, 5 females; age 16–24 years) completed a 12 × 25 m maximal effort trial to determine critical swimming speed. One week later, participants performed two separate trials in the moderate and severe domains. Capillary blood (1 mL) was collected pre- and post-exercise for DNA methylation profiling via reduced representation bisulfite sequencing. Global methylation and differentially methylated loci (DMLs) and regions (DMRs) were assessed using logistic regression. Exercise induced global hypomethylation regardless of intensity (severe domain: 0.25% difference; 95% CI: 0.023, 0.372; P_adj = 0.030; moderate domain: 0.17% difference; 95% CI: 0.012, 0.306; P_adj = 0.037). In contrast, DMLs and DMRs were largely intensity-specific, with <10% of DMLs and no DMRs shared between domains. Promoter DMRs were identified in immune-related genes: ARHGDIA (−13.5% in the severe domain) and RNF7 (+20.6% in the moderate domain). Although global methylation patterns were consistent between swimming trials, exercise intensity-specific DNA methylation signatures were detectable from capillary blood samples. These results highlight the potential of epigenetic profiling for personalised monitoring of training responses and athlete health.