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

Rattray, Nicholas J.W. and Trivedi, Drupad K. and Xu, Yun and Chandola, Tarani and Johnson, Caroline H. and Marshall, Alan D. and Mekli, Krisztina and Rattray, Zahra and Tampubolon, Gindo and Vanhoutte, Bram and White, Iain R. and Wu, Frederick C.W. and Pendleton, Neil and Nazroo, James and Goodacre, Royston (2019) Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. Nature Communications, 10 (1). 5027. ISSN 2041-1723

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    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.