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Regulation of p70S6k, GSK-3β, and calcineurin in rat striated muscle during aging

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Abstract

In this study we compared the content and phosphorylation levels of several molecules believed to regulate muscle hypertrophy and fiber type changes in the extensor digitorum longus (EDL), soleus, diaphragm, and heart of adult (6 months), aged (30 months), and very aged (36 months) Fischer 344 × Brown Norway rats. With aging, the mass of the EDL and soleus decreased significantly (~38% and ~36%, respectively), the diaphragm’s mass remained unchanged while the mass of the heart increased (~35%). Western blotting demonstrated that calcineurin (CnA), the 70-kDa ribosomal S6 kinase (p70S6k), glycogen synthase kinase-3β (GSK-3β), and the phosphorylated forms of GSK-3β and p70S6k (p-GSK-3βSer9 and p-p70S6kThr389) were regulated differently with aging and between muscle types. Total p70S6k, GSK-3β, and p-GSK-3βSer9 decreased in the aged-atrophic EDL and soleus while p-p70S6kThr389 increased. Although total p70S6k content diminished in the continuously active diaphragm, phosphorylation of p70S6k remained unchanged. Conversely, the expression of GSK-3β and p-GSK-3βSer9 increased in the diaphragm. With aging, the amount of p-p70S6kThr389 decreased ~56% in the heart while p-GSK-3β Ser9 increased ~193%. Interestingly, CnA content remained unchanged in the diaphragm, increased ~204% in the EDL, and decreased ~30% and ~65% with aging in the soleus and heart, respectively. These results indicate remarkable differences in the regulation of molecules thought to govern protein synthesis and changes in contractile protein expression.

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Authors and Affiliations

  1. Laboratory of Molecular Physiology, Department of Biological Sciences, Marshall University, Suite 311, Science Bldg, 1 John Marshall Drive, Huntington, WV, 2755-1090, USA

    R. S. Kinnard, D. B. Mylabathula, S. Uddemarri, K. M. Rice & E. R. Blough

  2. Department of Physiology, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, 2755-1090, USA

    G. L. Wright & E. R. Blough

Authors
  1. R. S. Kinnard
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  2. D. B. Mylabathula
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  3. S. Uddemarri
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  4. K. M. Rice
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  5. G. L. Wright
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  6. E. R. Blough
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Correspondence to E. R. Blough.

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Kinnard, R.S., Mylabathula, D.B., Uddemarri, S. et al. Regulation of p70S6k, GSK-3β, and calcineurin in rat striated muscle during aging. Biogerontology 6, 173–184 (2005). https://doi.org/10.1007/s10522-005-7953-6

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  • DOI: https://doi.org/10.1007/s10522-005-7953-6

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