Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice

Nathan K LeBrasseur, Teresa M. Schelhorn, Barbara L. Bernardo, Patricia G. Cosgrove, Paula M. Loria, Thomas A. Brown

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

The objective of this study was to examine the effects of short-term exercise training, myostatin inhibition (PF-354), and exercise + PF-354, all relative to a vehicle control, on performance and metabolic measures in 24-month-old mice. At study termination, PF-354-treated mice exhibited significantly greater muscle weights. Performance measures revealed that exercise + PF-354 increased treadmill running time and distance to exhaustion (more than twofold) and increased habitual activity. Measures of strength were not different; however, all treatment groups demonstrated more than 30% reductions in muscle fatigue. Metabolic measures showed that basal metabolic rates were higher in PF-354- and exercise + PF-354-treated mice, and exercise and exercise + PF-354 groups exhibited significantly greater insulin sensitivity. PF-354 was associated with decreased Smad3 phosphorylation and increased peroxisome proliferator-activated receptor gamma coactivator-1 a expression and, similar to exercise, decreased MuRF-1. The data suggest that the combination of exercise training and myostatin blockade may significantly improve physical function and whole-body metabolism in older individuals.

Original languageEnglish (US)
Pages (from-to)940-948
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume64
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

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Myostatin
Exercise
Basal Metabolism
Muscle Fatigue
Running
Insulin Resistance
Phosphorylation
Weights and Measures
Muscles

Keywords

  • Exercise capacity
  • Insulin resistance
  • Sarcopenia
  • Strength

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice. / LeBrasseur, Nathan K; Schelhorn, Teresa M.; Bernardo, Barbara L.; Cosgrove, Patricia G.; Loria, Paula M.; Brown, Thomas A.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 64, No. 9, 09.2009, p. 940-948.

Research output: Contribution to journalArticle

LeBrasseur, Nathan K ; Schelhorn, Teresa M. ; Bernardo, Barbara L. ; Cosgrove, Patricia G. ; Loria, Paula M. ; Brown, Thomas A. / Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2009 ; Vol. 64, No. 9. pp. 940-948.
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