Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET + LEU) would prevent disuse-induced atrophy and/or promote muscle recovery in aged mice and if these muscle responses correspond to changes in satellite cells and collagen remodeling. Aged mice (22–24 months) underwent 14 days of hindlimb unloading (HU) followed by 7 or 14 days of reloading (7 or 14 days RL). MET, LEU, or MET + LEU was administered via drinking water and were compared to Vehicle (standard drinking water) and ambulatory baseline. We observed that during HU, MET + LEU resolved whole body grip strength and soleus muscle specific force decrements caused by HU. Gastrocnemius satellite cell abundance was increased with MET + LEU treatment but did not alter muscle size during disuse or recovery conditions. Moreover, MET + LEU treatment alleviated gastrocnemius collagen accumulation caused by HU and increased collagen turnover during 7 and 14 days RL driven by a decrease in collagen IV content. Transcriptional pathway analysis revealed that MET + LEU altered muscle hallmark pathways related to inflammation and myogenesis during HU. Together, the dual treatment of MET and LEU was able to increase muscle function, satellite cell content, and reduce collagen accumulation, thus improving muscle quality during disuse and recovery in aging.

中文翻译：

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二甲双胍和亮氨酸在老化肌肉的废弃和恢复过程中增加卫星细胞和胶原蛋白重塑

废用后肌肉质量和力量的损失以及肌肉恢复受损通常随着年龄的增长而发生。二甲双胍 (MET) 和亮氨酸 (LEU) 在萎缩情况下单独显示出对骨骼肌的积极作用，但尚未进行联合评估，也未测试作为增强老化废用性萎缩后肌肉恢复的补救措施。本研究的目的是确定二甲双胍和亮氨酸 (MET + LEU) 的双重治疗是否会预防废用性萎缩和/或促进老年小鼠的肌肉恢复，以及这些肌肉反应是否与卫星细胞和胶原蛋白重塑的变化相对应. 老年小鼠（22-24 个月）经历了 14 天的后肢卸载（HU），然后是 7 或 14 天的重新加载（7 或 14 天 RL）。MET，低浓度铀，或 MET + LEU 通过饮用水给药，并与载体（标准饮用水）和流动基线进行比较。我们观察到，在 HU 期间，MET + LEU 解决了由 HU 引起的全身握力和比目鱼肌比力下降。MET + LEU 处理增加了腓肠肌卫星细胞丰度，但在废用或恢复条件下没有改变肌肉大小。此外，MET + LEU 治疗减轻了由 HU 引起的腓肠肌胶原蛋白积累，并在 RL 的 7 天和 14 天期间增加了胶原蛋白的更新，这是由 IV 型胶原蛋白含量的减少驱动的。转录通路分析显示，MET + LEU 改变了与 HU 期间炎症和肌生成相关的肌肉标志性通路。总之，MET 和 LEU 的双重治疗能够增加肌肉功能、卫星细胞含量、