TY - JOUR
T1 - Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice
AU - LeBrasseur, Nathan K.
AU - Schelhorn, Teresa M.
AU - Bernardo, Barbara L.
AU - Cosgrove, Patricia G.
AU - Loria, Paula M.
AU - Brown, Thomas A.
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
KW - Exercise capacity
KW - Insulin resistance
KW - Sarcopenia
KW - Strength
UR - http://www.scopus.com/inward/record.url?scp=68949108753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68949108753&partnerID=8YFLogxK
U2 - 10.1093/gerona/glp068
DO - 10.1093/gerona/glp068
M3 - Article
C2 - 19483181
AN - SCOPUS:68949108753
SN - 1079-5006
VL - 64
SP - 940
EP - 948
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 9
ER -