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    Molecular analyses provide insight into mechanisms underlying sarcopenia and myofibre denervation in old skeletal muscles of mice

    Access Status
    Fulltext not available
    Authors
    Barns, M.
    Gondro, C.
    Tellam, R.
    Crabb, Hannah
    Grounds, M.
    Shavlakadze, T.
    Date
    2014
    Type
    Journal Article
    
    Metadata
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    Citation
    Barns, M. and Gondro, C. and Tellam, R. and Radley-Crabb, H. and Grounds, M. and Shavlakadze, T. 2014. Molecular analyses provide insight into mechanisms underlying sarcopenia and myofibre denervation in old skeletal muscles of mice. The International Journal of Biochemistry & Cell Biology. 53: pp. 174-185.
    Source Title
    The International Journal of Biochemistry & Cell Biology
    DOI
    10.1016/j.biocel.2014.04.025
    ISSN
    1357-2725
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/3511
    Collection
    • Curtin Research Publications
    Abstract

    Molecular mechanisms that are associated with age-related denervation and loss of skeletal muscle mass and function (sarcopenia) are described for female C57Bl/6J mice aged 3, 15, 24, 27 and 29 months (m). Changes in mRNAs and proteins associated with myofibre denervation and protein metabolism in ageing muscles are reported, across the transition from healthy adult myofibres to sarcopenia that occurs between 15 and 24 m. This onset of sarcopenia at 24 m, corresponded with increased expression of genes associated with neuromuscular junction denervation including Chnrg, Chrnd, Ncam1, Runx1, Gadd45a and Myog. Sarcopenia in quadriceps muscles also coincided with increased protein levels for Igf1 receptor, Akt and ribosomal protein S6 (Rps6) with increased phosphorylation of Rps6 (Ser235/236) and elevated Murf1 mRNA and protein, but not Fbxo32: many of these changes are also linked to denervation. Global transcription profiling via microarray analysis confirmed these functional themes and highlighted additional themes that may be a consequence of pathology associated with sarcopenia, including changes in fatty acid metabolism, extracellular matrix structure and protein catabolism. Ageing was also associated with increased global gene expression variance, consistent with decreased control of gene regulation.

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