Muscle Mechanics in Metabolic Health and Longevity: The Biochemistry of Training Adaptations

Skeletal muscle is increasingly recognized as a dynamic endocrine organ whose secre-7 tome—particularly myokines—serves as a central hub for the coordination of systemic 8 metabolic health, inflammation, and tissue adaptation. This review integrates molecular, 9 cellular, and physiological evidence to elucidate how myokine signaling translates me-10 chanical and metabolic stimuli from exercise into biochemical pathways that regulate glu-11 cose homeostasis, lipid oxidation, mitochondrial function, and immune modulation. We 12 detail the duality and context-dependence of cytokine and myokine actions, emphasizing 13 the roles of key mediators such as IL-6, irisin, SPARC, FGF21, and BAIBA in orchestrating 14 cross-talk between muscle, adipose tissue, pancreas, liver, bone, and brain. Distinctions 15 between resistance and endurance training are explored, highlighting how each modality 16 shapes the myokine milieu and downstream metabolic outcomes through differential ac-17 tivation of AMPK, mTOR, and PGC-1α axes. The review further addresses the hormetic 18 role of reactive oxygen species, the importance of satellite cell dynamics, and the interplay 19 between anabolic and catabolic signaling in muscle quality control and longevity. We dis-20 cuss the clinical implications of these findings for metabolic syndrome, sarcopenia, and 21 age-related disease, and propose that the remarkable plasticity of skeletal muscle and its 22 secretome offers a powerful, multifaceted target for lifestyle interventions and future ther-23 apeutic strategies. An original infographic is presented to visually synthesize the complex 24 network of myokine-mediated muscle-organ interactions underpinning exercise-induced 25 metabolic health.