Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis

Leslie M. Baehr, Daniel W D West, George Marcotte, Andrea G. Marshall, Luis Gustavo De Sousa, Keith Baar, Sue C. Bodine

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength.

Original languageEnglish (US)
Pages (from-to)127-146
Number of pages20
JournalAging
Volume8
Issue number1
StatePublished - 2016

Fingerprint

Neuromuscular Junction
Skeletal Muscle
Muscle Strength
Hindlimb Suspension
Proteins
Muscles
Atrophic Muscular Disorders
Myogenin
Muscular Atrophy
Denervation
Proteasome Endopeptidase Complex
Hindlimb
Ubiquitin
RNA
Messenger RNA

Keywords

  • Aging
  • Anabolic resistance
  • Autophagy
  • Hindlimb unloading
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Baehr, L. M., West, D. W. D., Marcotte, G., Marshall, A. G., De Sousa, L. G., Baar, K., & Bodine, S. C. (2016). Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis. Aging, 8(1), 127-146.

Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis. / Baehr, Leslie M.; West, Daniel W D; Marcotte, George; Marshall, Andrea G.; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C.

In: Aging, Vol. 8, No. 1, 2016, p. 127-146.

Research output: Contribution to journalArticle

Baehr, LM, West, DWD, Marcotte, G, Marshall, AG, De Sousa, LG, Baar, K & Bodine, SC 2016, 'Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis', Aging, vol. 8, no. 1, pp. 127-146.
Baehr, Leslie M. ; West, Daniel W D ; Marcotte, George ; Marshall, Andrea G. ; De Sousa, Luis Gustavo ; Baar, Keith ; Bodine, Sue C. / Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis. In: Aging. 2016 ; Vol. 8, No. 1. pp. 127-146.
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