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1 Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Human Physiology Laboratory, Department of Health Sciences, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, MA, USA
2 Human Physiology Laboratory, Department of Health Sciences, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, MA, USA
3 Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: roger.fielding{at}tufts.edu.
In this study, we investigated the effect of age in the association of eukaryotic initiation factor 4E with eukaryotic initiation factor 4G (eIF4E-4G) 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 months old) and aged (O; 30 months old) Fischer 344 x Brown Norway rats were collected either immediately or 6 hr after HFES. eIF4E-4G association was elevated at 6 hr recovery in TA (1.9 ± 0.2-fold, P < 0.05) and both immediately and 6hr after exercise in Pla (2.1 ± 0.3-fold 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 hr after HFES in TA (5.0 ± 2.0-fold, P < 0.05) in Y rats. The phosphorylation of 
-isoform of GSK-3 was increased both immediately and 6 hr after contraction in both TA (1.6 ± 0.3-fold and 4.1 ± 0.8-fold, P < 0.05) and Pla (1.7 ± 0.2-fold and 2.1 ± 0.4-fold, P < 0.05) in Y rats and remained unaffected in O rats. The phosphorylation of 
-isoform of GSK-3 was observed only immediately after HFES in TA (1.5 ± 0.2-fold, P < 0.05) of Y rats. Overall, the association of eIF4E-4G and the phosphorylation of 4E-BP1 and GSK-3 are increased after HFES in adult animals 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.
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