PMID- 31722440
OWN - NLM
STAT- MEDLINE
DCOM- 20210202
LR  - 20211204
IS  - 1615-9861 (Electronic)
IS  - 1615-9853 (Linking)
VI  - 20
IP  - 5-6
DP  - 2020 Mar
TI  - Sarcopenia: Tilting the Balance of Protein Homeostasis.
PG  - e1800411
LID - 10.1002/pmic.201800411 [doi]
AB  - 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.
CI  - (c) 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Tan, Kuan Ting
AU  - Tan KT
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, 2 Medical Drive, MD9 Admin Office, Singapore, 117597, Singapore.
FAU - Ang, Seok-Ting Jamie
AU  - Ang SJ
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, 2 Medical Drive, MD9 Admin Office, Singapore, 117597, Singapore.
FAU - Tsai, Shih-Yin
AU  - Tsai SY
AUID- ORCID: 0000-0002-2834-6383
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, 2 Medical Drive, MD9 Admin Office, Singapore, 117597, Singapore.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20191204
PL  - Germany
TA  - Proteomics
JT  - Proteomics
JID - 101092707
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Aging
MH  - Animals
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Muscle, Skeletal/metabolism/physiopathology
MH  - *Proteostasis
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Sarcopenia/*etiology/metabolism/physiopathology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - AKT
OT  - ageing
OT  - mTOR
OT  - muscle atrophy
OT  - protein homeostasis
EDAT- 2019/11/14 06:00
MHDA- 2021/02/03 06:00
CRDT- 2019/11/14 06:00
PHST- 2019/04/17 00:00 [received]
PHST- 2019/11/04 00:00 [revised]
PHST- 2019/11/14 06:00 [pubmed]
PHST- 2021/02/03 06:00 [medline]
PHST- 2019/11/14 06:00 [entrez]
AID - 10.1002/pmic.201800411 [doi]
PST - ppublish
SO  - Proteomics. 2020 Mar;20(5-6):e1800411. doi: 10.1002/pmic.201800411. Epub 2019 Dec 
      4.