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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on May 29, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/glp068
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

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 and Thomas A. Brown

Cardiovascular, Metabolic & Endocrine Diseases, Pfizer Global Research & Development, Groton, Connecticut

Address correspondence to Nathan K. LeBrasseur, PT, PhD, Cardiovascular, Metabolic & Endocrine Diseases, Pfizer Global Research & Development, Eastern Point Road, MS 8220-3001, Groton, CT 06340. Email: nathan.lebrasseur{at}pfizer.com


  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{alpha} 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.

Keywords Sarcopenia; Insulin resistance; Strength; Exercise capacity

Received: February 23, 2009; Accepted: April 24, 2009

Decision Editor: Huber R. Warner, PhD


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