Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance
Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance
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DOI：
10.1093/gerona/glv033
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发表时间：
2016-04-01
影响因子：
5.1
通讯作者：
Peterson, Charlotte A.
中科院分区：
文献类型：
--
作者：
Lee, Jonah D.;Fry, Christopher S.;Peterson, Charlotte A.
虽然骨骼肌减少，即与年龄相关的肌肉质量和力量的丧失，既不会因为肌肉干细胞和卫星细胞的枯竭而加速，也不会加剧，但我们假设骨骼肌的适应能力将受到损害。为了验证这一假设，我们用他莫昔芬治疗4个月大的Pax7(Creer)-DTA小鼠耗尽卫星细胞，并在20个月后使足底肌肉承受2周的机械超负荷。我们发现，无论卫星细胞的含量如何，老年小鼠的肌纤维肥大都受到了损害。即使在没有生长的情况下，接受赋形剂治疗的小鼠也会出现再生反应，这在他莫昔芬治疗的小鼠中并不明显。此外，在没有生长的情况下发生了肌核增生，这被卫星细胞耗尽所阻止，这表明肌核增加不足以驱动肌纤维肥大。卫星细胞的耗尽增加了老化肌肉的细胞外基质含量，这是由于超负荷而加剧的，潜在地限制了肌纤维的生长。这些结果支持这样一种观点，即卫星细胞调节肌肉环境，它们在衰老过程中的丢失可能会导致纤维化，特别是在重塑期间。超负荷导致纤维类型成分的改善，不依赖于卫星细胞，这表明衰老的肌肉对运动诱导的氧化能力增强非常敏感，即使肥大反应受损。
Although sarcopenia, age-associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7(CreER)-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle-treated mice mounted a regenerative response, not apparent in tamoxifen-treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber-type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response.