Satellite cell attrition and skeletal muscle aging

Skeletal muscle aging involves the progressive decline in mass and function of muscle tissue, significantly impacting mobility and quality of life in older adults. Central to this process is the functional deterioration of SCs, the primary muscle stem cells responsible for regeneration. Aging impairs SC self-renewal, activation, proliferation, and differentiation through mechanisms including telomere attrition, mitochondrial dysfunction, epigenetic dysregulation, and aberrant signaling pathways such as Notch/Wnt and TGF-β. Additionally, the aged microenvironment—marked by chronic inflammation, oxidative stress, fibro-adipogenic infiltration, immune dysregulation, and vascular decline—further suppresses SC activity. Recent advances in multidisciplinary research, encompassing single-cell genomics, epigenetics, and bioengineering, have deepened our understanding of these mechanisms. Emerging interventions, such as nutritional strategies, exercise, pharmacological agents, cell therapy, and gene editing, offer promising avenues for restoring SC function and rejuvenating muscle regeneration. Future efforts should focus on integrated, personalized approaches to combat sarcopenia and improve healthspan.