title: Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.
abstract: Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults.
authors.affiliation: Division of Nutrition, Salt Lake City, UT, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Tanner
authors.affiliation: Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.
authors.forename: Lucille B
authors.initials: LB
authors.lastname: Brunker
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Centre for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Agergaard
authors.affiliation: Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Barrows
authors.affiliation: Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Briggs
authors.affiliation: Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.
authors.forename: Oh Sung
authors.initials: OS
authors.lastname: Kwon
authors.affiliation: Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Young
authors.affiliation: Cardiovascular Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.affiliation: Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Marcus
authors.affiliation: Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.|Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: LaStayo
authors.affiliation: Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.|Division of Nutrition, Salt Lake City, UT, USA.
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Drummond
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000601:Amino Acids, Essential / Q000378:metabolism; D001510:Bed Rest / Q000379:methods; D015415:Biomarkers / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005081:Exercise Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D059748:Proteolysis; D012333:RNA, Messenger / Q000378:metabolism; D013851:Thinness / Q000378:metabolism / Q000503:physiopathology*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D055815:Young Adult
chemical_list: D000601:Amino Acids, Essential; D015415:Biomarkers; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D055372:AMP-Activated Protein Kinases