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

• Published in: Nature communications Vol. 10; no. 1; pp. 5027 - 12
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.11.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 140/58; 631/1647/320; 692/4017; 692/53/2421; 692/53/2423; Aged; Aging; Aging - metabolism; Carnitine; Carnitine - metabolism; Confounding Factors, Epidemiologic; Discriminant Analysis; Economic policy; Energy Metabolism; Female; Frailty; Frailty - metabolism; Gas chromatography; Health; Humanities and Social Sciences; Humans; Male; Mass spectrometry; Mass spectroscopy; Metabolic Networks and Pathways; Metabolism; Metabolites; Metabolomics; Middle Aged; multidisciplinary; Older people; Phenotype; Phenotypes; Population studies; Principal Component Analysis; Regression analysis; Reproducibility of Results; Science; Science (multidisciplinary); Sustainability; Tocopherol; Vitamin E; Vitamin E - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12716-2

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. Risk of age-related chronic disorders and decrease in resilience is associated with ageing. Here the authors analyse the human blood metabolome and identify metabolites associated with frailty.