Regulation of p70S6k, GSK-3[beta], and calcineurin in rat striated muscle during aging

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 × Bro...

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Bibliographic Details
Published in:Biogerontology (Dordrecht) 2005-01, Vol.6 (3), p.173
Main Authors: Kinnard, R S, Mylabathula, D B, Uddemarri, S, Rice, K M, Wright, G L, Blough, E R
Format: Article
Language:English
Subjects:
Muscular system
Phosphorylation
Proteins
Regulation
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Summary: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 (p70^sup S6k^), glycogen synthase kinase-3β (GSK-3β), and the phosphorylated forms of GSK-3β and p70^sup S6k^ (p-GSK-3β^sup Ser9^ and p-p70^sup S6kThr389^) were regulated differently with aging and between muscle types. Total p70^sup S6k^, GSK-3β, and p-GSK-3β^sup Ser9^ decreased in the aged-atrophic EDL and soleus while p-p70^sup S6kThr389^ increased. Although total p70^sup S6k^ content diminished in the continuously active diaphragm, phosphorylation of p70^sup S6k^remained unchanged. Conversely, the expression of GSK-3β and p-GSK-3β^sup Ser9^ increased in the diaphragm. With aging, the amount of p-p70^sup S6kThr389^ decreased ~56% in the heart while p-GSK-3β^sup 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.[PUBLICATION ABSTRACT]
ISSN:1389-5729
1573-6768
DOI:10.1007/s10522-005-7953-6