Systemic Inflammation and Disruption of the Local Microenvironment Compromise Muscle Regeneration: Critical Pathogenesis of Autoimmune-Associated Sarcopenia.

Abstract

Unlabelled: Sarcopenia is defined by age-related reductions in muscle mass, strength, and physiological function, and it is especially prevalent among individuals with autoimmune diseases. Autoimmune disorders, characterized by immune dysregulation, cause systemic inflammation and damage to multiple tissues through unregulated immune activity. Research indicates that autoimmune diseases negatively impact skeletal muscle functions and may worsen the progression of sarcopenia. This viewpoint comprehensively discusses the pathogenesis and potential mechanism of sarcopenia in 3 autoimmune diseases: inflammatory bowel disease, rheumatoid arthritis, and type 1 diabetes mellitus. Mechanistically, chronic immune microenvironment alterations induce compartment-specific redistribution of leukocyte subsets and cytokine networks. These perturbations disrupt critical signaling pathways governing muscle protein synthesis, satellite cell activation, and mitochondrial bioenergetics, leading to impaired regeneration and accelerated sarcopenia progression. By delineating shared and distinct pathomechanisms across these models, this analysis reframes our understanding of immune-mediated muscle wasting. Beyond mechanistic insights, it establishes a translational framework for targeted therapies and highlights emerging research directions bridging immunology and age-related musculoskeletal decline.