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Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty

Author

Listed:
  • Nicholas J. W. Rattray

    (University of Manchester
    Yale University
    University of Strathclyde)

  • Drupad K. Trivedi

    (University of Manchester)

  • Yun Xu

    (University of Manchester
    University of Liverpool, Biosciences Building)

  • Tarani Chandola

    (University of Manchester)

  • Caroline H. Johnson

    (Yale University)

  • Alan D. Marshall

    (University of Manchester
    University of Edinburgh, Chrystal Macmillan Building, 15a George Square)

  • Krisztina Mekli

    (University of Manchester)

  • Zahra Rattray

    (University of Strathclyde)

  • Gindo Tampubolon

    (University of Manchester)

  • Bram Vanhoutte

    (University of Manchester
    University of Liverpool, Bedford Street South, University of Liverpool)

  • Iain R. White

    (University of Manchester
    University of Nova Gorica, Vipavska 13)

  • Frederick C. W. Wu

    (University of Manchester)

  • Neil Pendleton

    (University of Manchester Salford Royal Hospital)

  • James Nazroo

    (University of Manchester)

  • Royston Goodacre

    (University of Manchester
    University of Liverpool, Biosciences Building)

Abstract

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty.

Suggested Citation

  • Nicholas J. W. Rattray & Drupad K. Trivedi & Yun Xu & Tarani Chandola & Caroline H. Johnson & Alan D. Marshall & Krisztina Mekli & Zahra Rattray & Gindo Tampubolon & Bram Vanhoutte & Iain R. White & F, 2019. "Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12716-2
    DOI: 10.1038/s41467-019-12716-2
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