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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY
1Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer U.S. Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University; and 2Human Physiology Laboratory, Department of Health Sciences, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, Massachusetts
Submitted 15 April 2005 ; accepted in final form 18 November 2005
In this study, we investigated the effect of age on the association of eukaryotic initiation factor 4E (eIF4E) with eukaryotic initiation factor 4G (eIF4G), as well as the activity of its binding protein (4E-BP1) and the activity of glycogen synthase kinase-3 (GSK-3) after a single bout of rat hindlimb muscle contractile activity elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Tibialis anterior (TA) and plantaris (Pla) muscles from adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats were collected immediately or 6 h after HFES. eIF4E-eIF4G association was elevated at 6 h of recovery in TA (1.9 ± 0.2-fold, P < 0.05) and immediately and 6 h after exercise in Pla (2.1 ± 0.3- and 2.1 ± 0.7-fold, P < 0.05) in Y rats. No significant increase was observed in O rats. An increase in 4E-BP1 phosphorylation was observed only 6 h after HFES in TA (5.0 ± 2.0-fold, P < 0.05) in Y rats. Phosphorylation of GSK-3
was increased immediately and 6 h after contraction in TA (1.6 ± 0.3- and 4.1 ± 0.8-fold, P < 0.05) and Pla (1.7 ± 0.2- and 2.1 ± 0.4-fold, P < 0.05) in Y rats and remained unaffected in O rats. Phosphorylation of GSK-3
was observed only immediately after HFES in TA (1.5 ± 0.2-fold, P < 0.05) in Y rats. Overall, eIF4E-eIF4G association and phosphorylation of 4E-BP1 and GSK-3 are increased after HFES in adult, but not in aged, animals. These observations suggest that the anabolic response to muscle stimulation is attenuated with aging and may contribute to the limited capacity of hypertrophy in aged animals.
sarcopenia; exercise; signaling; hypertrophy
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