Endoplasmic reticulum stress in human skeletal muscle: any contribution to sarcopenia?
Endoplasmic reticulum stress in human skeletal muscle: any contribution to sarcopenia?
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DOI：
10.3389/fphys.2013.00236
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发表时间：
2013-09-03
影响因子：
4
通讯作者：
Deldicque L
中科院分区：
文献类型：
--
作者：
Deldicque L
骨骼肌对生命至关重要，因为它为运动、姿势和呼吸提供机械动力。除了这些重要功能外，骨骼肌还在全身代谢的调节中发挥重要作用，例如，葡萄糖稳态虽然随着年龄的增长，肌肉质量的逐渐减少似乎是不可避免的，但老年人尽可能保持最高的质量是至关重要的。很明显，肌肉减少症的起源是多因素的，但在本综述中，它被故意选择来评估一种特定的细胞应激，即内质网（ER）应激的可能贡献。有人提出，ER应激可以：（1）直接影响肌肉质量，因为长期和未解决的ER应激的一个结局是细胞死亡;（2）通过抑制雷帕霉素复合物1（mTORC 1）通路的哺乳动物靶点，间接产生合成代谢抗性状态。随着年龄的增长，许多未折叠蛋白质反应的关键组分，如伴侣蛋白和酶，表现出降低的表达和活性，导致ER功能失调，加速了通过ER相关降解丢弃蛋白质的速率。此外，ER应激可以阻断mTORC 1通路，该通路在响应营养素的合成代谢刺激和收缩活性中是必不可少的，从而参与衰老期间骨骼肌中众所周知的合成代谢抵抗状态。由于运动增加了几种分子伴侣的表达，它可以预测或恢复随年龄增长而丢失的未折叠蛋白质反应组分，从而降低ER应激水平。这一假设尚未得到验证，但它可能是老年人运动有益效果背后的一种新机制，不仅可以保护肌肉质量，还可以调节全身代谢。
Skeletal muscle is vital to life as it provides the mechanical power for locomotion, posture and breathing. Beyond these vital functions, skeletal muscle also plays an essential role in the regulation of whole body metabolism, e.g., glucose homeostasis. Although progressive loss of muscle mass with age seems unavoidable, it is critical for older people to keep the highest mass as possible. It is clear that the origin of sarcopenia is multifactorial but, in the present review, it was deliberately chosen to evaluate the likely contribution of one specific cellular stress, namely the endoplasmic reticulum (ER) stress. It is proposed that ER stress can: (1) directly impact muscle mass as one fate of prolonged and unresolved ER stress is cell death and; (2) indirectly create a state of anabolic resistance by inhibiting the mammalian target of rapamycin complex 1 (mTORC1) pathway. With age, many of the key components of the unfolded protein response, such as the chaperones and enzymes, display reduced expression and activity resulting in a dysfunctional ER, accelerating the rate of proteins discarded via the ER-associated degradation. In addition, ER stress can block the mTORC1 pathway which is essential in the response to the anabolic stimulus of nutrients and contractile activity thereby participating to the well-known anabolic resistance state in skeletal muscle during ageing. As exercise increases the expression of several chaperones, it could anticipate or restore the loss of unfolded protein response components with age and thereby reduce the level of ER stress. This hypothesis has not been tested yet but it could be a new mechanism behind the beneficial effects of exercise in the elderly not only for the preservation of muscle mass but also for the regulation of whole body metabolism.
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DOI：
10.1152/ajpendo.00038.2010
发表时间：
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影响因子：
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作者：
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DOI：
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