Muscle gradually loses its regenerative capacity with aging. Recent evidence highlights
age-related immune dysregulation as a key driver of satellite cell dysfunction and reduced
muscle regeneration. Timely elimination of apoptotic cells by phagocytes through efferocytosis is essential for tissue repair. Therefore, exploring age-related alterations in the
molecular machinery of efferocytosis and their impact on muscle regeneration is of great
relevance. This study examined the efferocytic machinery in the gastrocnemius muscle
tissue of young and aged rats after doxorubicin-induced acute myotoxicity and assessed the
potential of Vitamin B12-loaded chitosan nanoparticles (B12 CS NPS) to enhance efferocytosis and promote skeletal muscle injury repair in aged rats. Aged rats exhibited impaired
efferocytosis with a significant reduction in MerTK, PPARγ, and miR-124 expression, and
increased ADAM17 expression. B12 CS NPS administration significantly improved efferocytosis and reduced necrotic tissue areas, accompanied by increased MerTK, PPARγ, and
miR-124, and reduced ADAM17 expression. Supplementation with B12 CS NPS significantly enhanced satellite cell proliferation and differentiation, which was indicated by