Novak James S, Mázala Davi A G, Nearing Marie, Hindupur Ravi, Uapinyoying Prech, Habib Nayab F, Dickson Tessa, Ioffe Olga B, Harris Brent T, Fidelia-Lambert Marie N, Rossi Christopher T, Hill D Ashely, Wagner Kathryn R, Hoffman Eric P, Partridge Terence A
Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Department of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Aging Cell. 2021 Jul;20(7):e13411. doi: 10.1111/acel.13411. Epub 2021 Jun 5.
Age-related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third potential option is that the aged environment becomes inimical to the conduct of muscle regeneration. In the present study, we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle microenvironment such as to disfavor the myogenic function of these cells.
与年龄相关的肌肉质量和力量的丧失，普遍被认为是由于肌肉中驻留的卫星细胞执行其生肌功能的能力受限所致。这一观点包含两个尚未通过实验全面评估的概念。首先，它意味着在我们正常的日常活动过程中，我们会损伤并损失大量肌肉。其次，它表明肌肉修复机制在某种程度上被耗尽，从而限制了肌肉再生。第三个潜在的可能性是，衰老的环境对肌肉再生变得不利。在本研究中，我们使用已建立的人类肌肉异种移植模型，来测试从不同年龄尸体获取的肌肉样本，在移植到免疫缺陷小鼠体内后是否仍保持其生肌潜力。我们发现在所研究的高达78岁的年龄范围内，再生情况没有可测量的差异。此外，我们报告称，在我们的模型中，即使肌肉在死后11天进行移植，卫星细胞仍保持其生肌能力。我们得出结论，随着年龄增长肌肉质量的丧失并非归因于任何内在的生肌性丧失，而很可能是肌肉微环境中渐进性有害变化的反映，这种变化不利于这些细胞的生肌功能。
