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    Proteomic profiling reveals a severely perturbed protein expression pattern in aged skeletal muscle


    O'Connell, Kathleen and Gannon, Joan and Doran, Philip and Ohlendieck, Kay (2007) Proteomic profiling reveals a severely perturbed protein expression pattern in aged skeletal muscle. International Journal of Molecular Medicine, 20 (2). pp. 145-153. ISSN 1107-3756

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    Abstract

    Extended longevity is often accompanied by frailty and increased susceptibility to a variety of crippling disorders. One of the most striking features of human aging is sarcopenia, which is defined as the age-related decline in skeletal muscle mass and strength. Although various metabolic and functional defects in aging muscle fibres have been described over the last decade, it is not known whether a pathophysiological hierarchy exists within degenerative pathways leading to muscle wasting. Hence, in order to identify novel biomarkers of age-dependent skeletal muscle degeneration, we have here applied mass spectrometry-based proteomics for studying global muscle protein expression patterns. As a model system of sarcopenia, we have employed crude extracts from senescent rat gastrocnemius muscle, as compared to young adult tissue preparations. Using the highly sensitive protein dye Deep Purple for the analysis of the 2-D separated muscle proteome and peptide mass fingerprinting for the identification of individual protein spots, a differential expression pattern was observed for contractile proteins, metabolic factors, regulatory components and heat shock elements. A drastic increase was shown for alpha B-crystallin, myosin light chain MLC-1, phosphoglycerate kinase, adenylate kinase, triosephosphate isomerase, albumin, aconitase and nucleoside-diphosphate kinase in aged fibres. In contrast, the expression of pyruvate kinase, aldolase, creatine kinase, transferrin, alpha-tropomyosin and myosin light chain MLC-3 was decreased in old skeletal muscle. Comparative 2-D immunoblotting of selected candidate proteins has confirmed the effect of aging on the skeletal muscle proteome. These findings demonstrate a severely perturbed protein expression pattern in aged skeletal muscle, which reflects the underlying molecular alterations causing a drastic decline of muscle strength in the senescent organism. In the long-term, the systematic deduction of abnormal protein expression in aged muscle by proteomic profiling approaches may lead to the cataloguing of a cohort of novel therapeutic targets to treat muscular weakness in the aging population.

    Item Type: Article
    Keywords: aging; muscle degeneration; mass spectrometry; peptide mass fingerprinting; proteomics; sarcopenia;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7502
    Identification Number: https://doi.org/10.3892/ijmm.20.2.145
    Depositing User: Prof. Kay Ohlendieck
    Date Deposited: 11 Oct 2016 15:32
    Journal or Publication Title: International Journal of Molecular Medicine
    Publisher: Spandidos Publications
    Refereed: Yes
    Funders: Science Foundation Ireland (SFI), Health Research Board (HRB)
    URI:

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