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 journalArticlepeer-review

126 Scopus citations


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
Issue number9
StatePublished - Sep 2009


  • Exercise capacity
  • Insulin resistance
  • Sarcopenia
  • Strength

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology


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