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, Royston Goodacre

Research output: Contribution to journalArticle

3 Downloads (Pure)

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 languageEnglish
Article number5027
Number of pages12
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 5 Nov 2019

Fingerprint

carnitine
Carnitine
health
phenotype
Economics
Health
Tocotrienols
Phenotype
Metabolomics
economics
Public Policy
Health Policy
Vitamin E
Health Care Costs
Gas Chromatography-Mass Spectrometry
tocopherol
resilience
vulnerability
metabolites
Liquid chromatography

Keywords

  • global ageing
  • health care
  • social care
  • vitamin E pathways
  • metabolites
  • frailty
  • metabolomics

Cite this

Rattray, Nicholas J. W. ; Trivedi, Drupad K. ; Xu, Yun ; Chandola, Tarani ; Johnson, Caroline H. ; Marshall, Alan D. ; Mekli, Krisztina ; Rattray, Zahra ; Tampubolon, Gindo ; Vanhoutte, Bram ; White, Iain R. ; Wu, Frederick C. W. ; Pendleton, Neil ; Nazroo, James ; Goodacre, Royston. / Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. In: Nature Communications. 2019 ; Vol. 10, No. 1.
@article{113044747c5d4303b38261b9c3d46d46,
title = "Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty",
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.",
keywords = "global ageing, health care, social care, vitamin E pathways, metabolites, frailty, metabolomics",
author = "Rattray, {Nicholas J. W.} and Trivedi, {Drupad K.} and Yun Xu and Tarani Chandola and Johnson, {Caroline H.} and Marshall, {Alan D.} and Krisztina Mekli and Zahra Rattray and Gindo Tampubolon and Bram Vanhoutte and White, {Iain R.} and Wu, {Frederick C. W.} and Neil Pendleton and James Nazroo and Royston Goodacre",
year = "2019",
month = "11",
day = "5",
doi = "10.1038/s41467-019-12716-2",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
number = "1",

}

Rattray, NJW, Trivedi, DK, Xu, Y, Chandola, T, Johnson, CH, Marshall, AD, Mekli, K, Rattray, Z, Tampubolon, G, Vanhoutte, B, White, IR, Wu, FCW, 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, 5027. https://doi.org/10.1038/s41467-019-12716-2

Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. / Rattray, Nicholas J. W.; Trivedi, Drupad K.; Xu, Yun; Chandola, Tarani; Johnson, Caroline H.; Marshall, Alan D.; Mekli, Krisztina; Rattray, Zahra; Tampubolon, Gindo; Vanhoutte, Bram; White, Iain R.; Wu, Frederick C. W.; Pendleton, Neil; Nazroo, James; Goodacre, Royston.

In: Nature Communications, Vol. 10, No. 1, 5027, 05.11.2019.

Research output: Contribution to journalArticle

TY - JOUR

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

AU - Rattray, Nicholas J. W.

AU - Trivedi, Drupad K.

AU - Xu, Yun

AU - Chandola, Tarani

AU - Johnson, Caroline H.

AU - Marshall, Alan D.

AU - Mekli, Krisztina

AU - Rattray, Zahra

AU - Tampubolon, Gindo

AU - Vanhoutte, Bram

AU - White, Iain R.

AU - Wu, Frederick C. W.

AU - Pendleton, Neil

AU - Nazroo, James

AU - Goodacre, Royston

PY - 2019/11/5

Y1 - 2019/11/5

N2 - 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.

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.

KW - global ageing

KW - health care

KW - social care

KW - vitamin E pathways

KW - metabolites

KW - frailty

KW - metabolomics

U2 - 10.1038/s41467-019-12716-2

DO - 10.1038/s41467-019-12716-2

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5027

ER -