Journal of Applied Physiology  AJP: Regulatory, Integrative and Comparative Physiology
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J Appl Physiol 98: 557-564, 2005. First published October 1, 2004; doi:10.1152/japplphysiol.00811.2004
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Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation

David M. Thomson and Scott E. Gordon

Human Performance Laboratory, Department of Exercise and Sport Science, and Department of Physiology, East Carolina University, Greenville, North Carolina

Submitted 30 July 2004 ; accepted in final form 24 September 2004

Skeletal muscle mass declines with age, as does the potential for overload-induced fast-twitch skeletal muscle hypertrophy. Because 5'-AMP-activated protein kinase (AMPK) activity is thought to inhibit skeletal muscle protein synthesis and may therefore modulate muscle mass and hypertrophy, the purpose of this investigation was to examine AMPK phosphorylation status (a marker of AMPK activity) and its potential association with the attenuated overload-induced hypertrophy observed in aged skeletal muscle. One-week overload of fast-twitch plantaris and slow-twitch soleus muscles was achieved in young adult (8 mo; n = 7) and old (30 mo; n = 7) Fischer344 x Brown Norway male rats via unilateral gastrocnemius ablation. Significant (P ≤ 0.05) age-related atrophy (as measured by total protein content) was noted in plantaris and soleus control (sham-operated) muscles. In fast-twitch plantaris muscles, percent hypertrophy with overload was significantly attenuated with age, whereas AMPK phosphorylation status as determined by Western blotting [phospho-AMPK (Thr172)/total AMPK] was significantly elevated with age (regardless of loading status). There was also a main effect of loading on AMPK phosphorylation status in plantaris muscles (overload > control). Moreover, a strong and significant negative correlation (r = –0.82) was observed between AMPK phosphorylation status and percent hypertrophy in the overloaded plantaris muscles of all animals. In contrast to the plantaris, overload-induced hypertrophy of the slow-twitch soleus muscle was similar between ages, and AMPK phosphorylation in this muscle was also unaffected by age or overload. These data support the possibility that an age-related elevation in AMPK phosphorylation may partly contribute to the attenuated hypertrophic response observed with age in overloaded fast-twitch plantaris muscle.

fiber type; loading; sarcopenia; acetyl CoA carboxylase



Address for reprint requests and other correspondence: S. E. Gordon, Human Performance Laboratory, 363 Ward Sports Medicine Bldg., East Carolina Univ., Greenville, NC 27858 (E-mail: gordonsc{at}mail.ecu.edu)




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