Sarcopenia, defined as age-associated decline of muscle mass and function, is a risk factor for mortality and disability, and comorbid with several chronic diseases such as type II diabetes and cardiovascular diseases. Clinical trials showed that nutritional supplements had positive effects on muscle mass, but not on muscle function and strength, demonstrating our limited understanding of the molecular events involved in the ageing muscle. Protein homeostasis, the equilibrium between protein synthesis and degradation, is proposed as the major mechanism underlying the development of sarcopenia. As the key central regulator of protein homeostasis, the mammalian target of rapamycin (mTOR) is proposed to be essential for muscle hypertrophy. Paradoxically, sustained activation of mTOR complex 1 (mTORC1) is associated with a loss of sensitivity to extracellular signaling in the elderly. It is not understood why sustained mTORC1 activity, which should induce muscle hypertrophy, instead results in muscle atrophy. Here, recent findings on the implications of disrupting protein homeostasis on muscle physiology and sarcopenia development in the context of mTOR/protein kinase B (AKT) signaling are reviewed. Understanding the role of these molecular mechanisms during the ageing process will contribute towards the development of targeted therapies that will improve protein metabolism and reduce sarcopenia.

中文翻译：

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肌肉减少症：倾斜蛋白质稳态的平衡。

肌肉减少症定义为与年龄相关的肌肉质量和功能下降，是导致死亡和残疾的危险因素，并与多种慢性疾病（例如II型糖尿病和心血管疾病）并存。临床试验表明，营养补品对肌肉质量有积极影响，但对肌肉功能和强度却无益，这表明我们对与衰老肌肉有关的分子事件的了解有限。蛋白质稳态是蛋白质合成与降解之间的平衡，被认为是肌肉减少症发展的主要机制。作为蛋白质稳态的关键中枢调节剂，雷帕霉素（mTOR）的哺乳动物靶标被认为对肌肉肥大至关重要。矛盾的是，mTOR复合物1（mTORC1）的持续激活与老年人对细胞外信号的敏感性丧失有关。还不知道为什么持续的mTORC1活性会引起肌肉肥大，而该活动会引起肌肉肥大。在这里，综述了有关在mTOR /蛋白激酶B（AKT）信号传导中破坏蛋白质稳态对肌肉生理和肌肉减少症的影响的最新发现。了解这些分子机制在衰老过程中的作用将有助于开发靶向疗法，从而改善蛋白质代谢并减少肌肉减少症。综述了有关在mTOR /蛋白激酶B（AKT）信号传导中破坏蛋白质稳态对肌肉生理和肌肉减少症的影响的最新发现。了解这些分子机制在衰老过程中的作用将有助于开发靶向疗法，从而改善蛋白质代谢并减少肌肉减少症。综述了有关在mTOR /蛋白激酶B（AKT）信号传导中破坏蛋白质稳态对肌肉生理和肌肉减少症的影响的最新发现。了解这些分子机制在衰老过程中的作用将有助于开发靶向疗法，从而改善蛋白质代谢并减少肌肉减少症。