NAD + Enhanced Mesenchymal Stromal Cells Effect on Muscle Atrophy by Improving SIRT1‐Mediated Mitochondrial Function via NAMPT

作者：Jia Song, Yuting Sun, Nan Zang, Xue Liu, Jiamu Chen, Kewei Wang, Longqing Xia, Jun Chen, Ruxing Zhao, Fuqiang Liu, Xinguo Hou, Li Chen, Jun Cheng, Wenjian Zhang · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2025 · DOI：10.1002/jcsm.70142 · 被引用次数：4 · 研究领域：Sirtuins and Resveratrol in Medicine、Muscle Physiology and Disorders、Adipose Tissue and Metabolism

ABSTRACT Background Sarcopenia contributes to all‐cause mortality in the elderly; however, there is no specific treatment. Mesenchymal stromal cells (MSCs) ameliorate age‐related muscle loss and dysfunction and are potential therapeutic candidates for sarcopenia. However, their activity is easily affected by the surrounding environment and they are prone to replicative senescence during in vitro culture. Therefore, a drug that delays aging and enhances its function is required. Here, we investigated whether nicotinamide adenine dinucleotide (NAD + ) pretreatment enhances the therapeutic efficacy of MSCs on skeletal muscle atrophy and its underlying mechanism in a D‐galactose (D‐gal)–induced mouse model. Methods The administration of D‐gal to mice induces a range of age‐associated characteristics and is commonly used in research on age‐related muscle atrophy. Therefore, in this study, C57BL/6 J mice and C2C12‐differentiated myotubes exposed to D‐gal were used to explore the effects of MSCs/NAD + ‐MSCs on muscle atrophy. MSCs/NAD + ‐MSCs were injected into the skeletal muscles of the hind limbs every 7 days for six cycles. Treadmill running and grip strength tests were used to evaluate muscle strength. Muscle weight and fibre cross‐sectional area (CSA) were used to measure muscle mass. Multiomics analysis of quadriceps and NAD + ‐pretreated MSCs (NAD + ‐MSCs), Western blotting of muscle atrophy signalling, including Atrogin 1 and MuRF1, the mitochondrial complex, fatty acid oxi...