Exercise-derived exosomes mediate crosstalk between skeletal muscle, adipose tissue, and bone: mechanisms of inter-organ communication and tissue adaptation

Inter-organ communication among bone, skeletal muscle, and adipose tissue is essential for maintaining metabolic homeostasis and musculoskeletal integrity. Dysregulation of this crosstalk is closely associated with aging-related and metabolic diseases, including osteoporosis, sarcopenia, and obesity. With population aging and the rising prevalence of metabolic disorders, elucidating the mechanisms underlying bone-muscle-adipose interactions has become a critical focus in biomedical research. Emerging evidence highlights exercise-derived exosomes as key mediators of intercellular communication. These extracellular vesicles transport specific microRNAs and bioactive molecules that modulate signaling pathways across bone, skeletal muscle, and adipose tissue, thereby coordinating systemic metabolism and tissue remodeling. Exercise has been shown to regulate the biogenesis, release, and molecular cargo of exosomes, enhancing the synergistic function of these tissues and alleviating age-associated metabolic dysfunction and degeneration. Notably, exercise-induced exosomal miRNAs exhibit therapeutic potential by targeting pathways involved in inflammation, mitochondrial function, and anabolic-catabolic balance. This review summarizes current advances in the role of exercise-derived exosomes in bone-muscle-adipose crosstalk during aging and metabolic diseases, discusses their potential as novel therapeutic targets or biomarkers, and outlines key challenges and future research directions. These insights aim to provide a theoretical basis and practical guidance for the development of exercise-based interventions and aging-related disease therapies.