Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

J Physiol. 2015 Sep 15;593(18):4259-73. doi: 10.1113/JP270699. Epub 2015 Jul 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adult
  • Aged
  • Aging / metabolism
  • Aging / pathology*
  • Amino Acids, Essential / metabolism
  • Bed Rest / methods
  • Biomarkers / metabolism*
  • Exercise / physiology*
  • Exercise Therapy / methods
  • Female
  • Humans
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiology*
  • Protein Biosynthesis / physiology*
  • Proteolysis
  • RNA, Messenger / metabolism
  • Thinness / metabolism
  • Thinness / physiopathology*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Young Adult

Substances

  • Amino Acids, Essential
  • Biomarkers
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Muscle Proteins
  • RNA, Messenger
  • Tripartite Motif Proteins
  • TRIM63 protein, human
  • Ubiquitin-Protein Ligases
  • AMP-Activated Protein Kinases