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

Nicholas Rattray; Drupad Trivedi; Yun Xu; Tarani Chandola; Caroline Johnson; Alan Marshall; Krisztina Mekli; Zahra Rattray; Gindo Tampubolon; Bram Vanhoutte; Iain R. White; Frederick Wu; Neil Pendleton; James Nazroo; Royston Goodacre

doi:10.1038/s41467-019-12716-2

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

Nicholas Rattray, Drupad Trivedi, Yun Xu, Tarani Chandola, Caroline Johnson, Alan Marshall, Krisztina Mekli, Zahra Rattray, Gindo Tampubolon, Bram Vanhoutte, Iain R. White, Frederick Wu, Neil Pendleton, James Nazroo, Royston Goodacre

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	5027
Journal	Nature Communications
Volume	10
Issue number	1
Early online date	5 Nov 2019
DOIs	https://doi.org/10.1038/s41467-019-12716-2 https://doi.org/10.1038/s41467-019-12716-2
Publication status	Published - 5 Nov 2019

Research Beacons, Institutes and Platforms

Global Development Institute
Cathie Marsh Institute
Work and Equalities Institute
Manchester Institute for Collaborative Research on Ageing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Inequalities in later life frailty and wellbeing: an interdisciplinary approach to causality: Full bid
Nazroo, J. (PI), Burns, A. (CoI), Chandola, T. (CoI), Goodacre, R. (CoI), Horan, M. (CoI), Pendleton, N. (CoI), Tampubolon, G. (CoI) & Wu, F. (CoI)
1/11/11 → 31/12/16
Project: Research

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Rattray, N., Trivedi, D., Xu, Y., Chandola, T., Johnson, C., Marshall, A., Mekli, K., Rattray, Z., Tampubolon, G., Vanhoutte, B., White, I. R., Wu, F., Pendleton, N., Nazroo, J., & Goodacre, R. (2019). Metabolic dysregulation in Vitamin-E and carnitine shuttle energy mechanisms associate with human frailty. Nature Communications, 10(1), 5027. https://doi.org/10.1038/s41467-019-12716-2, https://doi.org/10.1038/s41467-019-12716-2

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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.",

author = "Nicholas Rattray and Drupad Trivedi and Yun Xu and Tarani Chandola and Caroline Johnson and Alan Marshall and Krisztina Mekli and Zahra Rattray and Gindo Tampubolon and Bram Vanhoutte and White, {Iain R.} and Frederick Wu and Neil Pendleton and James Nazroo and Royston Goodacre",

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Rattray, N, Trivedi, D, Xu, Y, Chandola, T, Johnson, C, Marshall, A, Mekli, K, Rattray, Z, Tampubolon, G , Vanhoutte, B, White, IR, Wu, F, Pendleton, N, Nazroo, J & Goodacre, R 2019, 'Metabolic dysregulation in Vitamin-E and carnitine shuttle energy mechanisms associate with human frailty', Nature Communications, vol. 10, no. 1, pp. 5027. https://doi.org/10.1038/s41467-019-12716-2, https://doi.org/10.1038/s41467-019-12716-2

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T1 - Metabolic dysregulation in Vitamin-E and carnitine shuttle energy mechanisms associate with human frailty

AU - Rattray, Nicholas

AU - Trivedi, Drupad

AU - Xu, Yun

AU - Chandola, Tarani

AU - Johnson, Caroline

AU - Marshall, Alan

AU - Mekli, Krisztina

AU - Rattray, Zahra

AU - Tampubolon, Gindo

AU - Vanhoutte, Bram

AU - White, Iain R.

AU - Wu, Frederick

AU - Pendleton, Neil

AU - Nazroo, James

AU - Goodacre, Royston

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AB - 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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DO - 10.1038/s41467-019-12716-2

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SN - 2041-1723

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SP - 5027

JO - Nature Communications

JF - Nature Communications

IS - 1

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

Abstract

Research Beacons, Institutes and Platforms

UN SDGs

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Inequalities in later life frailty and wellbeing: an interdisciplinary approach to causality: Full bid

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