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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.<\/jats:p>","DOI":"10.1002\/pmic.201800411","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T19:19:59Z","timestamp":1573672799000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Sarcopenia: Tilting the Balance of Protein Homeostasis"],"prefix":"10.1002","volume":"20","author":[{"given":"Kuan Ting","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine National University of Singapore  2 Medical Drive, MD9 Admin Office Singapore 117597 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok\u2010Ting Jamie","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine National University of Singapore  2 Medical Drive, MD9 Admin Office Singapore 117597 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2834-6383","authenticated-orcid":false,"given":"Shih\u2010Yin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine National University of Singapore  2 Medical Drive, MD9 Admin Office Singapore 117597 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12411"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169548"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afs194"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40200-017-0302-x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2013.11.025"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afq034"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2016.05.016"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-15-0533"},{"key":"e_1_2_7_9_1","first-page":"2","author":"Kamiya K.","year":"2017","journal-title":"J. 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