Document Detail


Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults.
MedLine Citation:
PMID:  22338078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Skeletal muscle atrophy during bed rest is attributed, at least in part, to slower basal muscle protein synthesis (MPS). Essential amino acids (EAA) stimulate mammalian target of rapamycin (mTORC1) signaling, amino acid transporter expression, and MPS and are necessary for muscle mass maintenance, but there are no data on the effect of inactivity on this anabolic mechanism. We hypothesized that bed rest decreases muscle mass in older adults by blunting the EAA stimulation of MPS through reduced mTORC1 signaling and amino acid transporter expression in older adults. Six healthy older adults (67 ± 2 yr) participated in a 7-day bed rest study. We used stable isotope tracers, Western blotting, and real-time qPCR to determine the effect of bed rest on MPS, muscle mTORC1 signaling, and amino acid transporter expression and content in the postabsorptive state and after acute EAA ingestion. Bed rest decreased leg lean mass by ∼4% (P < 0.05) and increased postabsorptive mTOR protein (P < 0.05) levels while postabsorptive MPS was unchanged (P > 0.05). Before bed rest acute EAA ingestion increased MPS, mTOR (Ser(2448)), S6 kinase 1 (Thr(389), Thr(421)/Ser(424)), and ribosomal protein S6 (Ser(240/244)) phosphorylation, activating transcription factor 4, L-type amino acid transporter 1 and sodium-coupled amino acid transporter 2 protein content (P < 0.05). However, bed rest blunted the EAA-induced increase in MPS, mTORC1 signaling, and amino acid transporter protein content. We conclude that bed rest in older adults significantly attenuated the EAA-induced increase in MPS with a mechanism involving reduced mTORC1 signaling and amino acid transporter protein content. Together, our data suggest that a blunted EAA stimulation of MPS may contribute to muscle loss with inactivity in older persons.
Authors:
Micah J Drummond; Jared M Dickinson; Christopher S Fry; Dillon K Walker; David M Gundermann; Paul T Reidy; Kyle L Timmerman; Melissa M Markofski; Douglas Paddon-Jones; Blake B Rasmussen; Elena Volpi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-14
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  302     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-02     Completed Date:  2012-08-03     Revised Date:  2013-09-30    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1113-22     Citation Subset:  IM    
Affiliation:
Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, USA. micah.drummond@hsc.utah.edu
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Aged
Amino Acid Transport Systems / genetics,  metabolism
Amino Acids, Essential / metabolism*
Bed Rest*
Humans
Middle Aged
Muscle, Skeletal / metabolism*
Muscular Atrophy / etiology*,  metabolism
Protein Biosynthesis / physiology
Proteins / genetics,  metabolism*
RNA, Messenger / analysis
Reference Values
Ribosomal Protein S6 / metabolism
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
K01 AG-038556/AG/NIA NIH HHS; K01 AG038556/AG/NIA NIH HHS; P30 AG-024832/AG/NIA NIH HHS; R01 AG-018311/AG/NIA NIH HHS; R01 AR-04987/AR/NIAMS NIH HHS; R01 AR049877/AR/NIAMS NIH HHS; UL1 RR-029876/RR/NCRR NIH HHS; UL1 TR000071/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems; 0/Amino Acids, Essential; 0/Proteins; 0/RNA, Messenger; 0/Ribosomal Protein S6; 0/mechanistic target of rapamycin complex 1; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.1/ribosomal protein S6 kinase, 70kD, polypeptide 1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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