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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·2019·Nature Communications
DOI 10.1038/s41467-019-12716-2PMC PMC6831565
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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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  • The effect of L-carnitine is possibly mediated by counteracting age-related declining L-carnitine levels which may limit fatty acid oxidation by mitochondria.

    “The effect is possibly mediated by counteracting age related declining L-carnitine levels which may limit fatty acid oxidation by mitochondria 161 .”

    From Hallmarks of aging: An expanding universe (2023) · cites this paper as [161]

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Metadata

Authors
Rattray, N. J. W., Trivedi, D. K., Xu, Y., Chandola, T., Johnson, C. H., Marshall, A. D., Mekli, K., Rattray, Z., Tampubolon, G., Vanhoutte, B., White, I. R., Wu, F. C. W., Pendleton, N., Nazroo, J., & Goodacre, R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-11-05
Volume
10
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-019-12716-2
PMC
PMC6831565
Cited by
101
References
15
Language
en
Licence
Funders
RCUK | Medical Research Council (190 MRC G1001375/1)

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