Vitamin B12-Loaded Chitosan Nanoparticles Promote Skeletal Muscle Injury Repair in Aged Rats via Amelioration of Aging-Suppressed Efferocytosis

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 <i>MerTK</i>, <i>PPARγ</i>, and miR-124 expression, and increased <i>ADAM17</i> expression. B12 CS NPS administration significantly improved efferocytosis and reduced necrotic tissue areas, accompanied by increased <i>MerTK</i>, <i>PPARγ</i>, and miR-124, and reduced <i>ADAM17</i> expression. Supplementation with B12 CS NPS significantly enhanced satellite cell proliferation and differentiation, which was indicated by upregulated expression of <i>Pax7</i>, <i>Myog</i>, and <i>MyoD</i>. These findings reveal that age-related alterations in regulatory molecules impair efferocytosis in aged muscle and demonstrate the potential of B12 CS NPs to enhance efferocytosis and improve skeletal muscle repair.