The repeated bout effect evokes the training-induced skeletal muscle cellular memory

Physical exercise is well-established as beneficial for health. With the 20th-century epidemiological transition, promoting healthy habits like exercise has become crucial for preventing chronic diseases. Stress can yield adaptive long-term benefits, potentially transmitted trans-generationally. Physical training exposes individuals to metabolic, thermal, mechanical, and oxidative stressors, activating cell signaling pathways that regulate gene expression and adaptive responses, thereby enhancing stress tolerance - a phenomenon known as hormesis. Muscle memory is the capacity of skeletal muscle to respond differently to environmental stimuli in an adaptive (positive) or maladaptive (negative) manner if the stimuli have been encountered previously. The Repeated Bout Effect encompasses our skeletal muscle capacity to activate an intrinsic protective mechanism that reacts to eccentric exercise-induced damage by activating an adaptive response that resists subsequent damage stimuli. Deciphering the molecular mechanism of this phenomenon would allow the incorporation of muscle memory in training programs for professional athletes, active individuals looking for the health benefits of exercise training, and patients with “exercise intolerance.” Moreover, enhancing the adaptive response of muscle memory could promote healing in individuals who traditionally do not recover after immobilization. The improvement could be part of an exercise program but could also be targeted pharmacologically. This review explores Repeated Bout Effect mechanisms: neural adaptations, tendon and muscle fiber property changes, extracellular matrix remodeling, and improved inflammatory responses.