Muscle-specific and age-related changes in protein synthesis and protein degradation in response to hindlimb unloading in rats

Leslie M. Baehr, Daniel W.D. West, Andrea G. Marshall, George R. Marcotte, Keith Baar, Sue C. Bodine

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss of muscle mass are highly debated. In particular, the extent to which disuse triggers decreases in protein synthesis or increases in protein degradation, and whether these changes are uniform across muscles or influenced by age, is unclear. We aimed to determine the impact of disuse on protein synthesis and protein degradation in lower limb muscles of varied function and fiber type in adult and old rats. Alterations in protein synthesis and degradation were measured in the soleus, medial gastrocnemius, and tibialis anterior (TA) muscles of adult and old rats subjected to hindlimb unloading (HU) for 3, 7, or 14 days. Loss of muscle mass was progressive during the unloading period, but highly variable (-9 to-38%) across muscle types and between ages. Protein synthesis decreased significantly in all muscles, except for the old TA. Atrophy-associated gene expression was only loosely associated with protein degradation as muscle RING finger-1, muscle atrophy F-box (MAFbx), and Forkhead box O1 expression significantly increased in all muscles, but an increase in proteasome activity was only observed in the adult soleus. MAFbx protein levels were significantly higher in the old muscles compared with adult muscles, despite the old having higher expression of microRNA-23a. These results indicate that adult and old muscles respond similarly to HU, and the greatest loss in muscle mass occurs in predominantly slow-twitch extensor muscles due to a concomitant decrease in protein synthesis and increase in protein degradation.

Original languageEnglish (US)
Pages (from-to)1336-1350
Number of pages15
JournalJournal of Applied Physiology
Volume122
Issue number5
DOIs
StatePublished - May 1 2017

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Keywords

  • Aging
  • MiR-23a
  • Muscle atrophy
  • Proteasome

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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