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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #181412
Title: AGE ASSOCIATED DECREASE IN CONTRACTION-INDUCED EIF4E-4G COMPLEX FORMATION IN SKELETAL MUSCLE

Author
item FUNAI, KATSUHIKO - BOSTON UNIVERSITY
item PARKINGTON, JASCHA - BOSTON UNIVERSITY
item CARAMBULA, SILVIA - TUFTS/HNRCA
item FIELDING, ROGER - TUFTS/HNRCA

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2005
Publication Date: 4/1/2006
Citation: Funai, K., Parkington, J., Carambula, S., Fielding, R. 2006. Age associated decrease in contraction-induced eif4e-4g complex formation in skeletal muscle. American Journal of Physiology. 290(4):R1080-6.

Interpretive Summary: Sarcopenia, the loss of skeletal muscle mass with age, can be improved with resistance exercise. However, the capacity of muscle growth (hypertrophy) has been reported to decline in aged animals and humans. The cellular changes in response to muscle contraction ultimately cause muscle cells to increase in size but the specific way that this happens and these processes are affected by age are not known. In this study, we looked at the effect of age on the regulation of metabolic pathways that turn on muscle protein synthesis in response to muscle action or contraction. Using a well characterized animal model for skeletal muscle aging, adult (6 months old) and aged (30 months old) Fischer 344 x Brown Norway rats were studied before and after activation (contraction) of their hind limbs designed to mimic a weightlifting protocol in humans. The results showed that the metabolic signals associated with turning on protein synthesis in the muscle cells are increased after HFES in adult animals but not in aged animals. These observations suggest that the protein synthesis in response to muscle contraction is attenuated with aging and may contribute to the limited capacity of muscle growth with aging. Future studies should investigate the metabolic causes of these changes and the resultant impact on skeletal muscle protein synthesis.

Technical Abstract: 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 alpha-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 beta-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.