Metabolomics

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


ABSTRACT: Global ageing has the potential to pose 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 and increasing dependency, resulting from disease, plays a central role in poor health in later life. Despite consensus on approaches to identify frailty there is limited understanding of the underlying biochemical changes caused by such a phenotype. Identification of the driving cellular mechanisms and ultimately, understanding of causal pathways central to the development of biomarker panels that can be applied to identify, monitor and facilitate intervention strategies are vital approaches to help reduce both individual and societal burden.
In this study, we present the first ever population level assessment of the biochemical phenotype associated with frailty, derived from comprehensive marker measurement. Analysis of serum from 1,191 older individuals (aged between 56 and 84 years old) was carried out using gas and liquid chromatography-mass spectrometry with metabolomics and biochemistry data being stratified across a modelled frailty index. Subsequent multivariate regression and network modelling identified 25 key metabolites (including three tocotrienols and six carnitines) in the differentiation of frail and non-frail phenotypes. These findings indicate the key role that the interaction of the carnitine shuttle and vitamin E metabolism play in modulating cellular energy production in relation to risk of frailty.

INSTRUMENT(S): LTQ Orbitrap XL (Thermo Scientific)

SUBMITTER: Nicholas Rattray  

PROVIDER: MTBLS598 | MetaboLights | 2019-09-06

REPOSITORIES: MetaboLights

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