Plasma cell‐free mitochondrial DNA declines in response to prolonged moderate aerobic exercise

Increased plasma cell‐free mitochondrial DNA (cf‐mDNA), a damage‐associated molecular pattern (DAMP) produced by cellular injury, contributes to neutrophil activation/inflammation in trauma patients and arises in cancer and autoimmunity. To further understand relationships between cf‐mDNA released by tissue injury, inflammation, and health benefits of exercise, we examined cf‐mDNA response to prolonged moderate aerobic exercise. Seven healthy moderately trained young men (age = 22.4 ± 1.2) completed a treadmill exercise trial for 90 min at 60% VO (2) max and a resting control trial. Blood was sampled immediately prior to exercise (0 min = baseline), during (+18, +54 min), immediately after (+90 min), and after recovery (R40). Plasma was analyzed for cf‐mDNA, IL‐6, and lactate. A significant difference in cf‐mDNA response was observed between exercise and control trials, with cf‐mDNA levels reduced during exercise at +54 and +90 (with or without plasma volume shift correction). Declines in cf‐mDNA were accompanied by increased lactate and followed by an increase in IL‐6, suggesting a temporal association with muscle stress and inflammatory processes. Our novel finding of cf‐mDNA decline with prolonged moderate treadmill exercise provides evidence for increased clearance from or reduced release of cf‐mDNA into the blood with prolonged exercise. These studies contrast with previous investigations involving exhaustive short‐term treadmill exercise, in which no change in cf‐mDNA levels were reported, and contribute to our understanding of differences between exercise‐ and trauma‐induced inflammation. We propose that transient declines in cf‐mDNA may induce health benefits, by reducing systemic inflammation.