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This Article Full Text Full Text (PDF) All Versions of this Article: 574/1/291    most recent jphysiol.2006.107490v3 jphysiol.2006.107490v2 jphysiol.2006.107490v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomson, D. M. Articles by Gordon, S. E. Search for Related Content PubMed PubMed Citation Articles by Thomson, D. M. Articles by Gordon, S. E. Related Collections Skeletal Muscle and Exercise

¹ Human Performance Laboratory, Department of Exercise and Sport Science, and Department of Physiology, East Carolina University, Greenville, NC 27858, USA

Impaired overload-induced protein synthesis and growth in aged fast-twitch skeletal muscle may result from diminished responsiveness of signalling intermediates controlling protein translation. Yet, potential age-related signalling decrements have never been examined in direct parallel with impaired overload-induced muscle growth in any model. To this end, we used Western blotting to examine the contents and phosphorylation states of mammalian target of rapamycin (mTOR) and its downstream translational signalling intermediates, 70 kDa ribosomal protein S6 kinase (S6k), ribosomal protein S6 (rpS6), eukaryotic elongation factor 2 (eEF2), and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in conjunction with impaired growth in 1 week overloaded fast-twitch plantaris muscles (via unilateral gastrocnemius ablation) of old (O; 30 months) versus young adult (YA; 8 months) male Fischer344 x Brown Norway rats. The significantly (P 0.05) diminished growth (assessed by total muscle protein content) in overloaded O muscles (5.6 ± 1.7 versus 19.3 ± 2.9% in YA) was accompanied by significant impairments in the phosphorylation states of mTOR (Ser²⁴⁴⁸), S6k (impaired at the mTOR-specific Thr³⁸⁹ residue but not at Thr⁴²¹/Ser⁴²⁴), rpS6 (Ser^235/236) and 4E-BP1 (gel shift), as well as deficits in total eEF2 accretion. Moreover, in overloaded muscles across both age groups, phospho-S6k at Thr³⁸⁹ (but not at Thr⁴²¹/Ser⁴²⁴), 4E-BP1 phosphorylation status, and total eEF2 accretion were all positively correlated with percentage muscle hypertrophy, and negatively correlated with the phosphorylation (Thr¹⁷²) of 5'-AMP-activated protein kinase (AMPK; which inhibits translational signalling and protein synthesis in young muscle at rest). As previously published by ourselves, AMPK was hyperphosphorylated in O versus YA muscles used in the current investigation. The present results provide solid evidence that impaired overload-induced growth in aged fast-twitch muscle may partly result from multiple-level decrements in signalling pathway(s) controlling protein translation, and also provide an initial indication that AMPK hyperactivation with age may potentially lie upstream of these decrements.

(Received 10 February 2006; accepted after revision 17 April 2006; first published online 20 April 2006)
Corresponding author S. E. Gordon: Human Performance Laboratory, 363 Ward Sports Medicine Building, East Carolina University, Greenville, NC 27858, USA.  Email: gordonsc{at}ecu.edu

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