Abstract：
Skeletal muscle wasting is the hallmark pathophysiological adaptation to unloading or disuse that demonstrates the dependency on frequent mechanical stimulation (e.g. muscle activation and subsequent loading) for homeostasis of normally load-bearing muscles. In the absence of mitigation strategies, no mammalian organism is resistant to muscle atrophy driven by unloading. Given the profound impact of unloading-induced muscle wasting on physical capacity, metabolic health and immune function; mitigation strategies during unloading and/or augmentation approaches during recovery have broad healthcare implications in settings of bed-bound hospitalization, cast immobilization and spaceflight. This topical review aims to: (1) provide a succinct, state-of-the-field summary of seminal and recent findings regarding the mechanisms of unloading-induced skeletal muscle wasting; (2) discuss unsuccessful vs. promising mitigation and recovery augmentation strategies; and (3) identify knowledge gaps ripe for future research. We focus on the rapid muscle atrophy driven by relatively short-term mechanical unloading/disuse, which is in many ways mechanistically distinct from both hypermetabolic muscle wasting and denervation-induced muscle atrophy. By restricting this discussion to mechanical unloading during which all components of the nervous system remain intact (e.g. without denervation models), mechanical loading requiring motor and sensory neural circuits in muscle remain viable targets for both mitigation and recovery augmentation. We emphasize findings in humans with comparative discussions of studies in rodents which enable elaboration of key mechanisms. We also discuss what is currently known about the effects of age and sex as biological factors, and both are highlighted as knowledge gaps and novel future directions due to limited research.
摘要：
骨骼肌萎缩是对卸载或废弃的标志性病理生理适应，证明了对频繁机械刺激（例如肌肉激活和随后的负荷）的依赖性，以维持正常负荷肌肉的稳态。在缺乏缓解策略的情况下，没有哺乳动物对卸载引起的肌肉萎缩有抵抗力。鉴于卸载引起的肌肉萎缩对身体能力的深远影响，代谢健康和免疫功能;恢复期间卸载和/或增强方法期间的缓解策略在卧床住院中具有广泛的医疗保健意义。铸造固定和太空飞行。这篇专题综述旨在：(1)提供一个简洁的，关于卸载引起的骨骼肌萎缩机制的开创性和最新发现的现场状态总结；（2）讨论不成功与有希望的缓解和恢复增强策略；(3)确定知识差距，为未来的研究做好准备。我们专注于由相对短期的机械卸载/废弃驱动的快速肌肉萎缩，这在许多方面与高代谢肌肉萎缩和去神经支配引起的肌肉萎缩在机械上是不同的。通过将此讨论限于机械卸载，在此期间神经系统的所有组件保持完整（例如，没有去神经模型），需要肌肉运动神经和感觉神经回路的机械负荷仍然是缓解和增强恢复的可行目标。我们通过对啮齿动物研究的比较讨论来强调人类的发现，这些研究可以详细说明关键机制。我们还讨论了目前已知的年龄和性别作为生物学因素的影响，由于有限的研究，两者都被强调为知识差距和新的未来方向。
