Non cell autonomous upregulation of CDKN2 transcription linked to progression of chronic hepatitis C disease

Authors

  • Mark W. Robinson,

    1. MRC – University of Glasgow Centre for Virus Research, Glasgow, UK
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    • Shared first authors.
  • Dagmara McGuinness,

    1. Section of Epigenetics, Institute of Cancer Sciences, MVLS, University of Glasgow, Glasgow, UK
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  • Rachael Swann,

    1. MRC – University of Glasgow Centre for Virus Research, Glasgow, UK
    2. Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
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  • Stephen Barclay,

    1. Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK
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  • Peter R. Mills,

    1. Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
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  • Arvind H. Patel,

    1. MRC – University of Glasgow Centre for Virus Research, Glasgow, UK
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  • John McLauchlan,

    Corresponding author
    1. MRC – University of Glasgow Centre for Virus Research, Glasgow, UK
    • Correspondence

      John McLauchlan, MRC-University of Glasgow Centre for Virus Research, 8 Church Street, Glasgow G11 5JR, Tel.: +0141 330 4028; fax: +0141 330 4029;

      e-mail: john.mclauchlan@glasgow.ac.uk

      Paul Gerard Shiels, University of Glasgow College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, McGregor Building, Level 2 Western Infirmary Glasgow, G11 6NT, Glasgow. Tel./fax: +0141 211 2138;

      e-mail: Paul.Shiels@glasgow.ac.uk

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  • Paul G. Shiels

    Corresponding author
    1. Section of Epigenetics, Institute of Cancer Sciences, MVLS, University of Glasgow, Glasgow, UK
    • Correspondence

      John McLauchlan, MRC-University of Glasgow Centre for Virus Research, 8 Church Street, Glasgow G11 5JR, Tel.: +0141 330 4028; fax: +0141 330 4029;

      e-mail: john.mclauchlan@glasgow.ac.uk

      Paul Gerard Shiels, University of Glasgow College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, McGregor Building, Level 2 Western Infirmary Glasgow, G11 6NT, Glasgow. Tel./fax: +0141 211 2138;

      e-mail: Paul.Shiels@glasgow.ac.uk

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    • Shared last authors.

  • This research was supported by funding from the UK Medical Research Council (MRC).

Summary

Chronic hepatitis C virus infection (C-HC) is associated with higher mortality arising from hepatic and extrahepatic disease. This may be due to accelerated biological aging; however, studies in C-HC have thus far been based solely on telomere length as a biomarker of aging (BoA). In this study, we have evaluated CDKN2 locus transcripts as alternative BoAs in C-HC. Our results suggest that C-HC induces non-cell-autonomous senescence and accelerates biological aging. The CDKN2 locus may provide a link between C-HC and increased susceptibility to age-associated diseases and provides novel biomarkers for assessing its impact on aging processes in man.

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