Skeletal Muscle Redox Signaling in Health and Disease: From Molecular Mechanisms to Therapeutic Exercise Strategies

Skeletal muscle plasticity is modulated by a delicate equilibrium between reactive oxygen species (ROS)-mediated signaling and oxidative distress. Although excessive oxidant accumulation impairs excitation-contraction coupling, accelerates fatigue, and contributes to muscle dysfunction, transient and compartmentalized ROS signals are now recognized as important modulators of mitochondrial biogenesis, metabolic remodeling, proteostasis, and tissue repair processes after contractile stress. This review synthesizes the biphasic nature of redox biology in exercise physiology, interpreting this duality through the paradigm of hormesis. We discuss modality-specific redox responses associated with endurance, resistance and high-intensity interval training, emphasizing that adaptive outcomes depend not on global redox shifts, but on spatiotemporally confined signaling cascades within specific nanodomains. Furthermore, we evaluate the controversial role of antioxidant supplementation, highlighting evidence that high-dose or poorly timed antioxidant intake attenuates specific exercise-induced adaptive responses. We further discuss how aging and chronic disease narrow the adaptive redox window by impairing mitochondrial quality control, inflammatory resolution, and recovery capacity. This paradigm supports a precision exercise strategy in which training modality, intensity, recovery, and nutritional interventions are aligned to preserve adaptive redox signaling while avoiding cumulative oxidative injury.