The role of AGEs in skeletal muscle atrophy and the beneficial effects of exercise.

Background: Advanced Glycation End Products (AGEs) are associated with the aging and atrophy of skeletal muscle. Their pathogenic mechanism mainly involves the binding of AGEs to their own receptors, which in turn triggers a series of pathological reactions. Exercise is considered an effective intervention method, as it can regulate the level of AGEs, thereby alleviating skeletal muscle atrophy. Objective: This study aims to review the latest research progress on skeletal muscle atrophy induced by AGEs and the beneficial effects of exercise. Methods: Relevant literature was searched from the establishment of databases (PubMed, Web of Science, Embase, and Scopus) to May 2025. The search terms were: "advanced glycation end products, receptor for advanced glycation end products, skeletal muscle, skeletal muscle atrophy, sarcopenia, aging, diabetes mellitus, obesity, exercise, aerobic training, resistance training, high-intensity interval training". Literature was included based on the following criteria: (a) Studies focusing on the mechanism of skeletal muscle atrophy induced by AGEs and the content related to exercise regulating AGEs levels; (b) Priority was given to literature published in the past 5 years with outstanding quality, relevance, or innovation. Finally, 138 pieces of literature were included for the review. Results and conclusions: AGEs bind to the receptor for advanced glycation end products (RAGE), which leads to a decrease in muscle protein synthesis, an increase in protein degradation, impairment of muscle fiber regeneration ability, and aggravation of myocyte apoptosis, thereby inducing or exacerbating skeletal muscle atrophy. Exercise can reduce the harmful effects of AGEs on muscle mass. Specifically, exercise can reduce the formation of AGEs by improving insulin sensitivity and glucose utilization, as well as alleviating chronic inflammation and oxidative stress. Additionally, exercise enhances the metabolic capacity of the kidneys for AGEs. These findings provide new insights for the development of drug regimens targeting the "AGEs-RAGE" axis and exercise interventions. In the future, in-depth clarification of the role of AGEs in the pathogenesis of skeletal muscle atrophy and the improvement mechanism mediated by exercise will provide an important basis for the prevention and treatment of sarcopenia related to aging and metabolic disorders.