Myostatin Inhibition Enhances the Effects of Exercise on Performance and Metabolic Outcomes in Aged Mice

被引：148

作者：

LeBrasseur, Nathan K. ^{[1
]}

Schelhorn, Teresa M. ^{[1
]}

Bernardo, Barbara L. ^{[1
]}

Cosgrove, Patricia G. ^{[1
]}

Loria, Paula M. ^{[1
]}

Brown, Thomas A. ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Cardiovasc Metab & Endocrine Dis, Groton, CT 06340 USA

来源：

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2009年 / 64卷 / 09期

关键词：

Sarcopenia; Insulin resistance; Strength; Exercise capacity; SKELETAL-MUSCLE MASS; PHYSICAL-ACTIVITY; INSULIN-RESISTANCE; PROLONGED ABSENCE; STRENGTH; ADULT; PHOSPHORYLATION; REGENERATION; IMPROVEMENT; DISABILITY;

D O I：

10.1093/gerona/glp068

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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.

引用

页码：940 / 948

页数：9

共 41 条

[1] The transcriptional coactivator PGC-1β drives the formation of oxidative type IIX fibers in skeletal muscle [J].

Arany, Zoltan ;

Lebrasseur, Nathan ;

Morris, Carl ;

Smith, Eric ;

Yang, Wenli ;

Ma, Yanhong ;

Chin, Sherry ;

Spiegelman, Bruce M. .

CELL METABOLISM, 2007, 5 (01) :35-46

[2] Selective activation of AMPK-PGC-1α or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation [J].

Atherton, PJ ;

Babraj, JA ;

Smith, K ;

Singh, J ;

Rennie, MJ ;

Wackerhage, H .

FASEB JOURNAL, 2005, 19 (02) :786-+

[3] Functional improvement of dystrophic muscle by myostatin blockade [J].

Bogdanovich, S ;

Krag, TOB ;

Barton, ER ;

Morris, LD ;

Whittemore, LA ;

Ahima, RS ;

Khurana, TS .

NATURE, 2002, 420 (6914) :418-421

[4] Myostatin as a therapeutic target for musculoskeletal disease [J].

Bradley, L. ;

Yaworsky, P. J. ;

Walsh, F. S. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (14) :2119-2124

[5] Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle [J].

Cuthbertson, D ;

Smith, K ;

Babraj, J ;

Leese, G ;

Waddell, T ;

Atherton, P ;

Wackerhage, H ;

Taylor, PM ;

Rennie, MJ .

FASEB JOURNAL, 2004, 18 (15) :422-+

[6] INSULIN-LIKE GROWTH FACTOR-I AND INSULIN-RESISTANCE IN SKELETAL-MUSCLES OF ADULT AND OLD RATS [J].

DARDEVET, D ;

SORNET, C ;

ATTAIX, D ;

BARACOS, VE ;

GRIZARD, J .

ENDOCRINOLOGY, 1994, 134 (03) :1475-1484

[7] Exercise-induced alterations in intramyocellular lipids and insulin resistance:: the athlete's paradox revisited [J].

Dube, John J. ;

Amati, Francesca ;

Stefanovic-Racic, Maja ;

Toledo, Frederico G. S. ;

Sauers, Sarah E. ;

Goodpaster, Bret H. .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2008, 294 (05) :E882-E888

[8] Ectopic expression of myostatin induces atrophy of adult skeletal muscle by decreasing muscle gene expression [J].

Durieux, Anne-Cecile ;

Amirouche, Adel ;

Banzet, Sebastien ;

Koulmann, Nathalie ;

Bonnefoy, Regis ;

Pasdeloup, Marielle ;

Mouret, Catherine ;

Bigard, Xavier ;

Peinnequin, Andre ;

Freyssenet, Damien .

ENDOCRINOLOGY, 2007, 148 (07) :3140-3147

[9] Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial [J].

Goodpaster, Bret H. ;

Chomentowski, Peter ;

Ward, Bryan K. ;

Rossi, Andrea ;

Glynn, Nancy W. ;

Delmonico, Matthew J. ;

Kritchevsky, Stephen B. ;

Pahor, Marco ;

Newman, Anne B. .

JOURNAL OF APPLIED PHYSIOLOGY, 2008, 105 (05) :1498-1503

[10] LOWER-EXTREMITY FUNCTION IN PERSONS OVER THE AGE OF 70 YEARS AS A PREDICTOR OF SUBSEQUENT DISABILITY [J].

GURALNIK, JM ;

FERRUCCI, L ;

SIMONSICK, EM ;

SALIVE, ME ;

WALLACE, RB .

NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (09) :556-561

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