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1Department of Health Sciences, Human Physiology Laboratory, Sargent College of Health and Rehabilitation Sciences, Boston University, and 2Center for the Molecular Stress Response, Boston University School of Medicine, Boston, Massachusetts 02215
Submitted 22 December 2003 ; accepted in final form 16 March 2004
With age, skeletal muscle experiences substantial atrophy and weakness. Although resistance training can increase muscle size and strength, the myogenic response to exercise and the capacity for muscle hypertrophy in older humans and animals is limited. In the present study, we assessed the ability of muscle contractile activity to activate cellular pathways involved in muscle cell growth and myogenesis in adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats. A single bout of rat hindlimb muscle contractile activity was elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Plantaris (Pla) and tibialis anterior (TA) muscles were assayed for mammalian target of rapamycin (mTOR), 70-kDa ribosomal protein S6 kinase (p70S6K), and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and total protein either at baseline, immediately after, or 6 h after HFES. mTOR phosphorylation was elevated in Pla (1.3 ± 0.3-fold, P < 0.05) immediately after HFES and to a lesser extent 6 h after HFES (0.6 ± 0.1-fold, P < 0.05) in O rats. Post-HFES, p70S6K phosphorylation increased 1.2 ± 0.3-fold in TA (P < 0.05) and remained elevated 6 h later (0.6 ± 0.2-fold, P < 0.05) in O rats. ERK phosphorylation was lower in O rats immediately after exercise in both TA (11.1 ± 2.9 vs. 2.1 ± 0.5-fold, P < 0.05) and Pla (6.5 ± 1.5 vs. 1.8 ± 0.5-fold, P < 0.05) and returned to baseline by 6 h in both Y and O rats. Phosphorylation of mTOR, p70S6K, and ERK1/2 are increased in skeletal muscle after a single bout of in situ muscle contractile activity in aged animals, and the response is less than that observed in adult animals. These observations suggest that the anabolic response to a single bout of contraction is attenuated with aging and may help explain the reduced capacity for hypertrophy in aged animals.
hypertrophy; extracellular related kinase; mammalian target of rapamycin; 70-kDa ribosomal protein S6 kinase
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