Aged individuals are at risk to experience slow and incomplete muscle recovery following periods of disuse atrophy. While several therapies have been employed to mitigate muscle mass loss during disuse and improve recovery, few have proven effective at both. Therefore, the purpose of this study was to examine the effectiveness of a uniquely developed secretome product (STEM) on aged skeletal muscle mass and function during disuse and recovery. Aged (22 months) male C57BL/6 were divided into PBS or STEM treatment (n = 30). Mice within each treatment were assigned to either ambulatory control (CON; 14 days of normal cage ambulation), 14 days of hindlimb unloading (HU), or 14 days of hindlimb unloading followed by 7 days of recovery (recovery). Mice were given an intramuscular delivery into the hindlimb muscle of either PBS or STEM every other day for the duration of their respective treatment group. We found that STEM-treated mice compared to PBS had greater soleus muscle mass, fiber cross-sectional area (CSA), and grip strength during CON and recovery experimental conditions and less muscle atrophy and weakness during HU. Muscle CD68 +, CD11b + and CD163 + macrophages were more abundant in STEM-treated CON mice compared to PBS, while only CD68 + and CD11b + macrophages were more abundant during HU and recovery conditions with STEM treatment. Moreover, STEM-treated mice had lower collagen IV and higher Pax7 + cell content compared to PBS across all experimental conditions. As a follow-up to examine the cell autonomous role of STEM on muscle, C2C12 myotubes were given STEM or horse serum media to examine myotube fusion/size and effects on muscle transcriptional networks. STEM-treated C2C12 myotubes were larger and had a higher fusion index and were related to elevated expression of transcripts associated with extracellular matrix remodeling. Our results demonstrate that STEM is a unique cocktail that possesses potent immunomodulatory and cytoskeletal remodeling properties that may have translational potential to improve skeletal muscle across a variety of conditions that adversely effect aging muscle.

老年人在废用性萎缩后面临着肌肉恢复缓慢且不完全的风险。虽然已经采用了多种疗法来减轻废用期间的肌肉质量损失并改善恢复，但很少有疗法被证明对两者都有效。因此，本研究的目的是检验独特开发的分泌组产品 (STEM) 对废弃和恢复期间老化骨骼肌质量和功能的有效性。将老年（22 个月）男性 C57BL/6 分为 PBS 或 STEM 治疗组（n  = 30）。每种治疗中的小鼠被分配到行走对照（CON；14天的正常笼内行走）、14天的后肢卸载（HU）或14天的后肢卸载随后7天的恢复（恢复）。在各自治疗组的持续时间内，每隔一天向小鼠后肢肌肉注射 PBS 或 STEM。我们发现，与 PBS 相比，STEM 治疗的小鼠在 CON 和恢复实验条件下具有更大的比目鱼肌质量、纤维横截面积 (CSA) 和握力，并且在 HU 期间肌肉萎缩和无力较少。与 PBS 相比，STEM 处理的 CON 小鼠的肌肉 CD68 +、CD11b + 和 CD163 + 巨噬细胞更丰富，而在 STEM 处理的 HU 和恢复条件下，只有 CD68 + 和 CD11b + 巨噬细胞更丰富。此外，在所有实验条件下，与 PBS 相比，STEM 处理的小鼠具有较低的 IV 型胶原蛋白和较高的 Pax7 + 细胞含量。作为检查 STEM 对肌肉的细胞自主作用的后续研究，C2C12 肌管被给予 STEM 或马血清培养基，以检查肌管融合/大小以及对肌肉转录网络的影响。经过 STEM 处理的 C2C12 肌管更大，融合指数更高，并且与细胞外基质重塑相关转录物表达升高有关。我们的结果表明，STEM 是一种独特的鸡尾酒，具有有效的免疫调节和细胞骨架重塑特性，可能具有在各种对衰老肌肉产生不利影响的条件下改善骨骼肌的转化潜力。