Intracellular and extracellular redox signals during exercise and aging

Regular physical activity enhances systemic health and resilience, partly through the generation of reactive oxygen species (ROS) that serve as key modulators of redox-sensitive signaling pathways. This review explores how redox signaling mediates both local and systemic responses to exercise, with particular focus on skeletal muscle and aging. We first examine the compartmentalized generation of ROS within myofibers, highlighting the distinct contributions of mitochondrial and NADPH oxidase systems and the context-dependent nature of oxidative eustress versus distress. We then detail how redox signals initiate adaptive responses that extend beyond muscle through the release of exerkines, cytokines, peptides, and metabolites, and their packaging within extracellular vesicles (EVs). These circulating factors facilitate interorgan communication and reinforce systemic redox homeostasis. Aging disrupts these processes, leading to impaired redox signaling, neuromuscular degeneration, and diminished responsiveness to exercise. Notably, animal models such as Sod1-deficient mice underscore the importance of neuronal redox control in sarcopenia. Finally, we highlight how exercise-induced EVs may counteract age-associated dysfunction by delivering redox-regulatory molecules to distant tissues. Understanding the molecular interplay between redox signals and systemic adaptation offers promising avenues for therapeutic strategies targeting metabolic and neuromuscular decline in aging.