Center for Muscle Biology, University of Kentucky, Lexington, Kentucky.
Department of Athletic Training and Clinical Nutrition, University of Kentucky, Lexington, Kentucky.
J Appl Physiol (1985). 2022 Sep 1;133(3):637-646. doi: 10.1152/japplphysiol.00083.2022. Epub 2022 Jul 21.
The diaphragm is the main skeletal muscle responsible for inspiration and is susceptible to age-associated decline in function and morphology. Satellite cells in diaphragm fuse into unperturbed muscle fibers throughout life, yet their role in adaptations to hypoxia in diaphragm is unknown. Given their continual fusion, we hypothesize that satellite cell depletion will negatively impact adaptations to hypoxia in the diaphragm, particularly with aging. We used the Pax7:R26R genetic mouse model of inducible satellite cell depletion to investigate diaphragm responses to hypoxia in adult (6 mo) and aged (22 mo) male mice. The mice were subjected to normobaric hypoxia at 10% [Formula: see text] or normoxia for 4 wk. We showed that satellite cell depletion had no effect on diaphragm muscle fiber cross-sectional area, fiber-type distribution, myonuclear density, or regulation of extracellular matrix in either adult or aged mice. Furthermore, we showed lower muscle fiber cross-sectional area with hypoxia and age (main effects), while extracellular matrix content was higher and satellite cell abundance was lower with age (main effect) in diaphragm. Lastly, a greater number of Pax3-mRNA cells was observed in diaphragm muscle of satellite cell-depleted mice independent of hypoxia (main effect), potentially as a compensatory mechanism for the loss of satellite cells. We conclude that satellite cells are not required for diaphragm muscle adaptations to hypoxia in either adult or aged mice. Satellite cells show consistent fusion into diaphragm muscle fibers throughout life, suggesting a critical role in maintaining homeostasis. Here, we report identical diaphragm adaptations to hypoxia with and without satellite cells in adult and aged mice. In addition, we propose that the higher number of Pax3-positive cells in satellite cell-depleted diaphragm muscle acts as a compensatory mechanism.
横膈膜是主要的骨骼肌肉,负责吸气,容易随着年龄的增长而导致功能和形态下降。横膈膜中的卫星细胞在整个生命过程中融合到未受干扰的肌肉纤维中,但它们在横膈膜对缺氧的适应中的作用尚不清楚。鉴于它们持续融合,我们假设卫星细胞耗竭将对横膈膜对缺氧的适应产生负面影响,尤其是在衰老时。我们使用 Pax7:R26R 遗传诱导卫星细胞耗竭的小鼠模型来研究成年(6 个月)和老年(22 个月)雄性小鼠的横膈膜对缺氧的反应。将小鼠置于 10% [Formula: see text]的常压缺氧或常氧中 4 周。结果表明,卫星细胞耗竭对成年或老年小鼠的横膈膜肌肉纤维横截面积、纤维型分布、肌核密度或细胞外基质的调节均无影响。此外,我们发现缺氧和年龄(主要影响)导致肌肉纤维横截面积降低,而年龄(主要影响)导致细胞外基质含量增加和卫星细胞数量减少。最后,无论是否缺氧(主要影响),在卫星细胞耗竭的小鼠的横膈膜肌肉中都观察到更多的 Pax3-mRNA 细胞,这可能是卫星细胞耗竭的代偿机制。我们得出结论,卫星细胞不是成年或老年小鼠横膈膜肌肉对缺氧适应所必需的。卫星细胞在整个生命过程中持续融合到横膈膜肌肉纤维中,表明它们在维持内稳态方面具有关键作用。在这里,我们报告了成年和老年小鼠在有或没有卫星细胞的情况下,横膈膜对缺氧的适应是相同的。此外,我们提出在卫星细胞耗竭的横膈膜肌肉中,更高数量的 Pax3 阳性细胞作为代偿机制。