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Metabolic biomarkers of ageing in C57BL/6J wild-type and flavin-containing monooxygenase 5 (FMO5)-knockout mice

Title: Metabolic biomarkers of ageing in C57BL/6J wild-type and flavin-containing monooxygenase 5 (FMO5)-knockout mice
Authors: Varshavi, D
Scott, FH
Varshavi, D
Veeravalli, S
Phillips, IR
Veselkov, K
Strittmatter, N
Takats, Z
Shephard, EA
Everett, JR
Item Type: Journal Article
Abstract: It was recently demonstrated in mice that knockout of the flavin-containing monooxygenase 5 gene, Fmo5, slows metabolic ageing via pleiotropic effects. We have now used an NMR-based metabonomics approach to study the effects of ageing directly on the metabolic profiles of urine and plasma from male, wild-type C57BL/6J and Fmo5-/- (FMO5 KO) mice back-crossed onto the C57BL/6J background. The aim of this study was to identify metabolic signatures that are associated with ageing in both these mouse lines and to characterize the age-related differences in the metabolite profiles between the FMO5 KO mice and their wild-type counterparts at equivalent time points. We identified a range of age-related biomarkers in both urine and plasma. Some metabolites, including urinary 6-hydroxy-6-methylheptan-3-one (6H6MH3O), a mouse sex pheromone, showed similar patterns of changes with age, regardless of genetic background. Others, however, were altered only in the FMO5 KO, or only in the wild-type mice, indicating the impact of genetic modifications on mouse ageing. Elevated concentrations of urinary taurine represent a distinctive, ageing-related change observed only in wild-type mice.
Issue Date: 9-Apr-2018
Date of Acceptance: 19-Mar-2018
URI: http://hdl.handle.net/10044/1/62254
DOI: https://dx.doi.org/10.3389/fmolb.2018.00028
ISSN: 2296-889X
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Molecular Biosciences
Volume: 5
Copyright Statement: © 2018 Varshavi, Scott, Varshavi, Veeravalli, Phillips, Veselkov, Strittmatter, Takats, Shephard and Everett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the or iginal publication in this journal is cited, in accordance with accepted academ ic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 634402
Keywords: 6-hydroxy-6-methyl-heptan-3-one
C57BL/6J
FMO5 KO
ageing
metabolomics
metabonomics
plasma
urine
Publication Status: Published
Conference Place: Switzerland
Article Number: ARTN 28
Appears in Collections:Division of Surgery
Faculty of Medicine



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