Molecular basis of muscle wasting and emerging therapeutic strategies targeting degenerative muscle disorders

Abstract

Muscle degenerative conditions, including sarcopenia, muscular dystrophies, and trauma-induced muscle loss, severely compromise mobility, metabolism, and overall health. These disorders result from multifactorial causes such as imbalances in protein homeostasis, satellite cell dysfunction, mitochondrial stress, and chronic inflammation. Central molecular regulators such as FOXO, AMPK, mTOR, and the myostatin/SMAD axis, play pivotal roles in driving muscle atrophy. Current regenerative strategies seek to restore muscle structure and function through stem cell-based therapies (MSCs, iPSC-derived muscle progenitors, and satellite cells), gene editing, exosome-mediated delivery, and biomaterial scaffolds. Emerging evidence highlights the therapeutic potential of engineered exosomes, pro-regenerative cytokines, and biomimetic scaffolds in enhancing angiogenesis, myogenesis, and immune modulation. In parallel, advances in multi-omics and artificial intelligence are accelerating the identification of key molecular targets and the development of personalized interventions. Combination therapies that integrate cellular, molecular, and structural approaches demonstrate synergistic benefits for improving outcomes. This review summarizes current knowledge of the molecular mechanisms underlying muscle degeneration and discusses emerging therapeutic strategies that hold promise for effective muscle regeneration.

Keywords: Exosomes; Muscle atrophy; Muscle regeneration; Muscle wasting; Sarcopenia; Stem cell-based therapy.