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

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, Frederick C. W. Wu, Neil Pendleton, James Nazroo and Royston Goodacre
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Nicholas J. W. Rattray: University of Manchester
Drupad K. Trivedi: University of Manchester
Yun Xu: University of Manchester
Tarani Chandola: University of Manchester
Caroline H. Johnson: Yale University
Alan D. Marshall: University of Manchester
Krisztina Mekli: University of Manchester
Zahra Rattray: University of Strathclyde
Gindo Tampubolon: University of Manchester
Bram Vanhoutte: University of Manchester
Iain R. White: University of Manchester
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

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12716-2

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