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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.
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1 School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK; Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
2 School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK
3 School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK; Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Biosciences Building, Liverpool, UK
4 Cathie Marsh Institute for Social Research, University of Manchester, Manchester, UK
5 Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA
6 Cathie Marsh Institute for Social Research, University of Manchester, Manchester, UK; School of Social and Political Science, University of Edinburgh, Chrystal Macmillan Building, 15a George Square, Edinburgh, UK
7 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
8 Cathie Marsh Institute for Social Research, University of Manchester, Manchester, UK; Department of Sociology, Eleanor Rathbone Building, University of Liverpool, Bedford Street South, University of Liverpool, Liverpool, UK
9 School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK; Laboratory for Environmental and Life Sciences, University of Nova Gorica, Vipavska 13, Nova Gorica, Slovenia
10 Faculty of Medical and Human Sciences, Institute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
11 Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester Salford Royal Hospital, Manchester, UK