Molecular and Cellular Mechanisms Linking Chronic Kidney Disease and Sarcopenia in Aging: An Integrated Perspective

Jing Chang,1,* Yuer Liang,2,* Pingping Sun,1 Xiangyang Fang,1 Qianmei Sun2 1Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Nephrology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qianmei Sun, Email [email protected]: Chronic kidney disease (CKD) and sarcopenia are prevalent conditions among the aging population, contributing significantly to morbidity and mortality. CKD exacerbates sarcopenia through complex molecular and cellular mechanisms, including chronic inflammation, oxidative stress, uremic toxin accumulation, protein-energy wasting, and hormonal dysregulation. This review explores the interplay between CKD and sarcopenia, focusing on key pathways such as mTOR signaling, the AMPK-FOXO axis, and myostatin/activin pathways that regulate muscle protein metabolism. Additionally, mitochondrial dysfunction and impaired autophagy emerge as critical contributors to muscle wasting. Clinical implications include identifying biomarkers such as interleukin-6, tumor necrosis factor-alpha, myostatin, and Klotho for diagnosis and monitoring, while potential therapeutic strategies involve targeting the AMPK/mTOR pathway, enhancing mitochondrial function, and inhibiting myostatin activity. Emerging approaches, including multi-omics technologies and AI-driven personalized treatment models, offer innovative solutions for understanding and managing the CKD-sarcopenia axis. This review underscores the need for integrated therapeutic strategies and multidisciplinary collaboration to mitigate muscle wasting and improve outcomes in CKD patients. By bridging molecular insights with clinical applications, this work aims to inform future research and translational efforts in addressing this critical healthcare challenge.Keywords: chronic kidney disease, sarcopenia, sarcopenia pathophysiology, therapeutic targets