School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Department of Environmental Health Sciences, Yale School of Public Health, Yale University, 60 College Street, New Haven, CT, 06520, USA.
Nat Commun. 2019 Nov 5;10(1):5027. 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.
全球老龄化给医疗和社会保健成本带来了巨大的经济负担。使更多的老年人更长久地保持健康是未来健康、社会和经济政策可持续性的关键。虚弱和相关的弹性下降在晚年健康不良中起着核心作用。在这项研究中，我们对与虚弱相关的代谢表型进行了人群水平评估。使用液体和气相色谱-质谱代谢组学分析了来自 1191 名老年人（年龄在 56 岁至 84 岁之间）的血清，并随后进行了纵向验证（在 786 名受试者上进行），并根据旨在定量总结脆弱性的虚弱指数进行分层。通过多元回归、网络建模和 mROC 建模，我们确定了 12 种有意义的代谢物（包括三种生育三烯酚和六种肉碱），它们可区分虚弱和非虚弱表型。我们的研究提供了证据，表明肉碱穿梭和维生素 E 途径的失调与虚弱的风险有关。
