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J Gerontol A Biol Sci Med Sci. 2009 Sep;64(9):940-8. doi: 10.1093/gerona/glp068. Epub 2009 May 29.

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

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  • 1Cardiovascular, Metabolic & Endocrine Diseases, Pfizer Global Research & Development, Eastern Point Road, MS 8220-3001, Groton, CT 06340, USA. nathan.lebrasseur@pfizer.com


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-1alpha 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.

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