Open Exercise Promotes Tissue Regeneration: Mechanisms Involved and Therapeutic Scope

Exercise confers systemic benefits and can promote tissue regeneration and repair across multiple organs. This review synthesizes evidence that exercise activates stem and progenitor cells to drive regeneration in skeletal muscle, the nervous system, and the cardiovascular/vascular systems. It details how exercise-induced stem cell activation confers protection in pathological and aging contexts, and delineates key molecular mediators including growth factors (e.g., IGF1, VEGF), signaling pathways (e.g., PI3K–Akt, MAPK, Notch), oxidative stress/ROS dynamics, metabolic reprogramming, and non-coding RNAs (miRNAs and lncRNAs). The review also highlights therapeutic strategies that target exercise-responsive pathways and molecules (e.g., IGF1, PI3K, microRNAs) to mimic exercise benefits when physical training is not feasible. Key points: (1) Exercise-enhanced regeneration of skeletal muscle, vasculature, and nervous system depends on activation of stem/progenitor cells; (2) Signaling pathways, oxidative stress, metabolic factors, and non-coding RNAs underlie exercise-driven stem cell activation; (3) Pharmacologically targeting key regulators of exercise-induced stem cell activation shows therapeutic promise.