Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice.
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.
LeBrasseur
Nathan K
NK
Cardiovascular, Metabolic & Endocrine Diseases, Pfizer Global Research & Development, Eastern Point Road, MS 8220-3001, Groton, CT 06340, USA. nathan.lebrasseur@pfizer.com
Schelhorn
Teresa M
TM
Bernardo
Barbara L
BL
Cosgrove
Patricia G
PG
Loria
Paula M
PM
Brown
Thomas A
TA
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004734:Energy Metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism; D055435:Myostatin / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D051900:Smad3 Protein / Q000378:metabolism
D055435:Myostatin; D051900:Smad3 Protein; C497791:Smad3 protein, mouse