Skeletal muscle stretching as a mechanotransductive trigger for myokine release: A narrative review

Skeletal muscle functions as an endocrine organ by releasing myokines—cytokines and peptides that mediate systemic physiological adaptations. This review synthesizes evidence establishing mechanical stretching (active/passive) as a potent mechanotransductive stimulus for myokine secretion. Key pathways include integrin-mediated signaling, stretch-activated ion channels (Piezo/TRP), and mechanosensitive transcriptional regulators (YAP/TAZ), which activate MAPK, calcium-dependent kinases, and other cascades to modulate myokine gene expression. We highlight stretch-responsive myokines (IL-6, irisin, myostatin, BDNF, SPARC) and their roles in metabolism, tissue repair, and inflammation. Clinical implications for aging, metabolic disease, and rehabilitation are discussed, emphasizing how targeted stretching protocols may harness myokine-mediated benefits in mobility-limited populations. Future research directions include optimizing stretch "dosing" and elucidating tissue-specific myokine actions.