The Role of Exercise in Maintaining the Health of Muscle Satellite Cells and Tissue Regeneration

Background and Objective: Muscle satellite cells (SCs), a population of adult stem cells residing beneath the basal lamina of skeletal muscle fibers, serve as the primary mediators of postnatal muscle growth, adaptation, and regeneration. Despite their quiescent state under homeostatic conditions, these cells retain remarkable proliferative and myogenic potential that can be activated in response to mechanical, metabolic, and biochemical stimuli. Exercise represents one of the most potent physiological modulators of satellite cell dynamics; however, the precise molecular and cellular mechanisms by which different exercise modalities — including resistance, endurance, and high-intensity interval training — influence SC pool maintenance, activation kinetics, self-renewal capacity, and functional output remain incompletely characterized. This review aims to synthesize current evidence regarding the effects of acute and chronic exercise on satellite cell biology, with particular emphasis on niche signaling, epigenetic regulation, mitochondrial quality control, and age-related alterations in SC function. Methods: A comprehensive and systematic review of peer-reviewed literature published between ۲۰۱۵ and ۲۰۲۵ was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases. Search terms included combinations of “satellite cells,” “exercise,” “skeletal muscle regeneration,” “myogenesis,” “muscle stem cells,” “resistance training,” “endurance exercise,” “aging,” and “epigenetics.” Studies were selected based on methodological rigor, relevance to the central topic, and publication in high-impact journals with impact factor ≥ ۴.۰. Both human and animal model studies were included, with critical appraisal of experimental design, sample characteristics, and outcome measures. Results: Accumulated evidence from molecular, cellular, and integrative physiological investigations demonstrates that exercise exerts multifaceted and context-dependent effects on satellite cell biology. Acute resistance exercise transiently activates quiescent SCs through mechanical force transduction, hepatocyte growth factor (HGF) release, nitric oxide (NO) signaling, and upregulation of the paired box transcription factor Pax۷. Chronic resistance training has been shown to expand the SC pool by ۳۰–۱۰۰% in young adults, enhancing myonuclear accretion and fiber hypertrophy. Endurance exercise preferentially modulates SC mitochondrial biogenesis and metabolic reprogramming via PGC-۱α-dependent pathways, thereby preserving SC oxidative capacity and self-renewal fidelity. High-intensity interval training (HIIT) activates both myogenic and metabolic regulatory networks, with synergistic effects on SC activation and systemic rejuvenation factors. Furthermore, exercise-induced systemic factors — including irisin, IGF-۱, IL-۶, and extracellular vesicles — create a pro-myogenic circulatory milieu that sustains SC niche integrity. In the context of aging, exercise partially attenuates the hallmarks of satellite cell senescence, including impaired Notch signaling, elevated p۳۸α MAPK activity, increased oxidative stress, and epigenetic drift toward fibrogenic lineages. Emerging evidence also highlights the role of exercise in modulating the gut-muscle axis and systemic inflammation, both of which indirectly regulate SC behavior. Conclusion: Exercise training, across multiple modalities, constitutes a powerful, non-pharmacological intervention for preserving and enhancing satellite cell health, myogenic capacity, and skeletal muscle regenerative potential throughout the lifespan. The beneficial effects of exercise on SC biology are mediated through an intricate network of mechanical, hormonal, immunological, metabolic, and epigenetic mechanisms. These findings carry substantial implications for the development of exercise-based therapeutic strategies targeting sarcopenia, muscular dystrophies, cachexia, and age-related regenerative decline. Future investigations employing single-cell transcriptomics, spatial proteomics, and longitudinal human cohort designs are warranted to further delineate the exercise dose-response relationships governing satellite cell function and to translate these insights into precision exercise medicine

کلیدواژه ها:

Satellite cells ، Skeletal muscle regeneration ، Exercise training ، Myogenesis ، Sarcopenia