title: Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults.
abstract: 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.affiliation: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, USA. micah.drummond@hsc.utah.edu
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Drummond
authors.forename: Jared M
authors.initials: JM
authors.lastname: Dickinson
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.forename: Dillon K
authors.initials: DK
authors.lastname: Walker
authors.forename: David M
authors.initials: DM
authors.lastname: Gundermann
authors.forename: Paul T
authors.initials: PT
authors.lastname: Reidy
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Timmerman
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Markofski
authors.forename: Douglas
authors.initials: D
authors.lastname: Paddon-Jones
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
mesh_terms: D000367:Age Factors; D000368:Aged; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D000601:Amino Acids, Essential / Q000378:metabolism*; D001510:Bed Rest; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
chemical_list: D026905:Amino Acid Transport Systems; D000601:Amino Acids, Essential; D046912:Multiprotein Complexes; D011506:Proteins; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1