Metabolomics identifies metabolic dysregulation as driver behind human frailty

Posted on: 14 April 2021 by Prof Roy Goodacre in Case studies

Image showing ageing

Ever increasing ageing populations can pose substantial economic burden on health and society and therefore there is a strong desire to ensure healthy ageing into later life.

Frailty can be permanent or temporary and the affected individual can return to a more resilient state.  It is known that major stress events such as loss of a partner are associated with frailty; however, the pathophysiological effects are that drive the frailty phenotype.

Increased risk of frailty is unfortunately a defining characteristic of biological ageing. However, little is known about underlying biological mechanisms.  The CMR with collaborators from the Universities of Manchester, Strathclyde, Yale and St. Andrews undertook research that identified two features of metabolic dysregulation, related to vitamin E and carnitine shuttle energy mechanisms, that are related to increased risk of frailty.

In this study published in Nature Communications MS-based metabolomics, combining LC-MS and GC-MS, was applied to the blood serum of 1200 elderly people. Chemometrics and machine learning with rigorous statistical validation was used to categorise bio-signatures of frailty.  This resulted in a panel of 12 metabolites being able to distinguish frail from non-frail people 80% of the time.  Importantly, this was validated in a follow up study of near 800 individuals.

This research has opened up the application of enabling technologies such as biological mass spectrometry within the realm of biogerontology (the study of the biological processes of ageing) and further applications will deliver benefits in helping to understand, prevent, cure or minimise age-related impairments.

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