Circulating Nucleosomes Respond to Moderate Aerobic Exercise: A Pilot Study in Healthy Individuals and Cancer Patients

Background/Objectives: Circulating nucleosomes containing H3.1 represent a distinct fraction of extracellular chromatin. Although strenuous exercise is known to increase circulating extracellular chromatin components, it remains unclear whether H3.1-containing nucleosomes also respond to moderate physiological stress and whether this response varies with the underlying biological condition. Methods: Sixteen healthy subjects and 13 subjects with cancer completed a standardized 5 km walking exercise. Venous blood samples were collected immediately before and after exercise, and circulating H3.1-containing nucleosomes were quantified in K2-EDTA plasma with an automated immunoassay. Within-group and between-group comparisons were performed using non-parametric tests. Relative exercise-induced changes and age-adjusted analyses were evaluated as sensitivity analyses. Results: Circulating H3.1-containing nucleosome concentrations increased significantly after exercise in both healthy subjects (p < 0.0001) and those with cancer (p = 0.001). Cancer patients displayed higher baseline concentrations (p = 0.0056), whereas post-exercise concentrations were comparable between groups (p = 0.840). The absolute exercise-induced increase was significantly higher in healthy subjects (p = 0.028). This difference was confirmed when the response was expressed relative to individual baseline concentrations (median increase: 124.7% [IQR 63.9–191.5%] vs. 36.5% [20.6–42.0%]; p = 0.0009) and persisted after age adjustment (p = 0.0046). Conclusions: Circulating H3.1-containing nucleosomes respond to moderate aerobic exercise, with distinct patterns in healthy subjects and those with cancer. These preliminary findings support further investigation of H3.1-containing nucleosomal chromatin as a dynamic marker of the biological response to exercise.