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Sarcopenia: Tilting the Balance of Protein Homeostasis
Author(s) -
Tan Kuan Ting,
Ang SeokTing Jamie,
Tsai ShihYin
Publication year - 2020
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201800411
Subject(s) - sarcopenia , mtorc1 , pi3k/akt/mtor pathway , skeletal muscle , homeostasis , context (archaeology) , muscle hypertrophy , glucose homeostasis , protein degradation , protein kinase b , muscle atrophy , biology , mechanistic target of rapamycin , ageing , mtorc2 , endocrinology , medicine , diabetes mellitus , microbiology and biotechnology , signal transduction , insulin resistance , paleontology
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.