Mitochondrial Inflammation and Muscle Aging: Targeting the Inflammatory Microenvironment in Sarcopenic Muscle.

Abstract

Sarcopenia is an age-related progressive degenerative disorder of skeletal muscle characterized by declining muscle mass, strength, and function. Increasing evidence indicates that chronic low-grade inflammation plays an important contributory role in its pathogenesis. The inflammatory microenvironment contributes to sarcopenia through complex interactions involving cellular senescence, mitochondrial dysfunction, and sustained inflammatory signaling, forming a self-reinforcing pathological cycle within skeletal muscle. This review synthesizes current evidence on the molecular mechanisms underlying inflammation-driven sarcopenia, with particular emphasis on how inflammatory signaling disrupts protein turnover and satellite cell metabolism. In addition, exercise is examined as a precision "hormone-like" intervention tailored to different sarcopenia phenotypes, highlighting the distinct mechanisms through which resistance training, aerobic exercise, and combined training modulate the senescence-associated phenotype and inflammatory responses. The review further evaluates anti-inflammatory therapeutic strategies, including nutritional interventions, pharmacotherapy, and acupuncture. These approaches improve muscle health by restoring immune balance, enhancing mitochondrial function, modulating the gut-muscle axis, reducing oxidative stress, and promoting the clearance of senescent cells. Finally, emerging precision medicine frameworks and multi-omics strategies that may support individualized sarcopenia management are discussed. Overall, this review provides an integrated perspective on inflammatory signaling in sarcopenia and outlines potential therapeutic strategies targeting the inflammatory microenvironment, offering insights for future research and clinical management.