PMID- 16627569
OWN - NLM
STAT- MEDLINE
DCOM- 20060905
LR  - 20230417
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 574
IP  - Pt 1
DP  - 2006 Jul 1
TI  - Impaired overload-induced muscle growth is associated with diminished 
      translational signalling in aged rat fast-twitch skeletal muscle.
PG  - 291-305
AB  - 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 <or= 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 (Ser235/236) 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.
FAU - Thomson, David M
AU  - Thomson DM
AD  - Human Performance Laboratory, 363 Ward Sports Medicine Building, East Carolina 
      University, Greenville, NC 27858, USA.
FAU - Gordon, Scott E
AU  - Gordon SE
LA  - eng
GR  - R15 AG025101/AG/NIA NIH HHS/United States
GR  - AG025101/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060420
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Muscle Proteins)
SB  - IM
MH  - Adaptation, Physiological
MH  - Aging/*metabolism
MH  - Animals
MH  - Cumulative Trauma Disorders/*metabolism
MH  - Muscle Fibers, Fast-Twitch/*metabolism
MH  - Muscle Proteins/*metabolism
MH  - Muscle, Skeletal/*physiopathology
MH  - *Protein Modification, Translational
MH  - Rats
MH  - Rats, Inbred F344
MH  - Signal Transduction
PMC - PMC1817794
EDAT- 2006/04/22 09:00
MHDA- 2006/09/06 09:00
PMCR- 2007/07/01
CRDT- 2006/04/22 09:00
PHST- 2006/04/22 09:00 [pubmed]
PHST- 2006/09/06 09:00 [medline]
PHST- 2006/04/22 09:00 [entrez]
PHST- 2007/07/01 00:00 [pmc-release]
AID - jphysiol.2006.107490 [pii]
AID - 10.1113/jphysiol.2006.107490 [doi]
PST - ppublish
SO  - J Physiol. 2006 Jul 1;574(Pt 1):291-305. doi: 10.1113/jphysiol.2006.107490. Epub 
      2006 Apr 20.