Metabolic Biomarkers of Ageing in C57BL/6J Wild-Type and Flavin-Containing Monooxygenase 5 (FMO5)-Knockout Mice

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2018 Apr 25

PMID 29686991

Citations 10

Authors

Dorsa Varshavi

Flora H Scott

Dorna Varshavi

Sunil Veeravalli

Ian R Phillips

Kirill Veselkov

Nicole Strittmatter

Zoltan Takats

Elizabeth A Shephard

Jeremy R Everett

Affiliations

Soon will be listed here.

Abstract

It was recently demonstrated in mice that knockout of the flavin-containing monooxygenase 5 gene, , 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 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.

Citing Articles

A Cross-Sectional Quantitative Metabolomics Study Evidencing the Metabolic Signature in Six Organs during a 14-Week High-Fat High-Sucrose and Standard Diet in Mice.

Drevet Mulard E, Guibert S, Mey A, Lefevre C, Chauvin M, Pinteur C Nutrients. 2024; 16(6).

PMID: 38542714 PMC: 10975117. DOI: 10.3390/nu16060803.

Metabolomics to Study Human Aging: A Review.

Martins C, Magalhaes S, Almeida I, Neto V, Rebelo S, Nunes A Curr Mol Med. 2023; 24(4):457-477.

PMID: 37026499 DOI: 10.2174/1566524023666230407123727.

Chronic treatment with baicalein alleviates behavioural disorders and improves cerebral blood flow via reverting metabolic abnormalities in a J20 transgenic mouse model of Alzheimer's disease.

Zhang L, Wong L, Wong P, Shen W, Yang S, Huang L Brain Behav Immun Health. 2023; 28:100599.

PMID: 36817510 PMC: 9931920. DOI: 10.1016/j.bbih.2023.100599.

Editorial: Genomic alteration landscapes of aging, metabolic disorders, and cancer: Emerging overlaps and clinical importance.

Dhanjal J, Kalra R, Tomar D, Ajay A Front Genet. 2023; 13:1102953.

PMID: 36685844 PMC: 9852706. DOI: 10.3389/fgene.2022.1102953.

Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of mice, decreases plasma cholesterol and epididymal fat deposition.

Veeravalli S, Varshavi D, Scott F, Varshavi D, Pullen F, Veselkov K Front Physiol. 2022; 13:859681.

PMID: 36003643 PMC: 9393927. DOI: 10.3389/fphys.2022.859681.

References

Rock F, Mueller S, Weimar U, Rammensee H, Overath P . Comparative analysis of volatile constituents from mice and their urine. J Chem Ecol. 2006; 32(6):1333-46. DOI: 10.1007/s10886-006-9091-2. View

Li J, Saric J, Yap I, Utzinger J, Holmes E . Metabonomic investigations of age- and batch-related variations in female NMRI mice using proton nuclear magnetic resonance spectroscopy. Mol Biosyst. 2013; 9(12):3155-65. DOI: 10.1039/c3mb70215d. View

Dona A, Kyriakides M, Scott F, Shephard E, Varshavi D, Veselkov K . A guide to the identification of metabolites in NMR-based metabonomics/metabolomics experiments. Comput Struct Biotechnol J. 2016; 14:135-53. PMC: 4821453. DOI: 10.1016/j.csbj.2016.02.005. View

Veselkov K, Mirnezami R, Strittmatter N, Goldin R, Kinross J, Speller A . Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer. Proc Natl Acad Sci U S A. 2014; 111(3):1216-21. PMC: 3903245. DOI: 10.1073/pnas.1310524111. View

Kwak J, Grigsby C, Rizki M, Preti G, Koksal M, Josue J . Differential binding between volatile ligands and major urinary proteins due to genetic variation in mice. Physiol Behav. 2012; 107(1):112-20. DOI: 10.1016/j.physbeh.2012.06.008. View

Veselkov K, Vingara L, Masson P, Robinette S, Want E, Li J . Optimized preprocessing of ultra-performance liquid chromatography/mass spectrometry urinary metabolic profiles for improved information recovery. Anal Chem. 2011; 83(15):5864-72. DOI: 10.1021/ac201065j. View

Stoyanova I . Ghrelin: a link between ageing, metabolism and neurodegenerative disorders. Neurobiol Dis. 2014; 72 Pt A:72-83. DOI: 10.1016/j.nbd.2014.08.026. View

Dieterle F, Ross A, Schlotterbeck G, Senn H . Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. Anal Chem. 2006; 78(13):4281-90. DOI: 10.1021/ac051632c. View

Barr D, Wilder L, Caudill S, Gonzalez A, Needham L, Pirkle J . Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005; 113(2):192-200. PMC: 1277864. DOI: 10.1289/ehp.7337. View

10.

Kurien B, Everds N, Scofield R . Experimental animal urine collection: a review. Lab Anim. 2004; 38(4):333-61. DOI: 10.1258/0023677041958945. View

11.

Phelan M, McLean L, Hurst J, Beynon R, Lian L . Comparative study of the molecular variation between 'central' and 'peripheral' MUPs and significance for behavioural signalling. Biochem Soc Trans. 2014; 42(4):866-72. DOI: 10.1042/BST20140082. View

12.

Williams R, Lenz E, Lowden J, Rantalainen M, Wilson I . The metabonomics of aging and development in the rat: an investigation into the effect of age on the profile of endogenous metabolites in the urine of male rats using 1H NMR and HPLC-TOF MS. Mol Biosyst. 2006; 1(2):166-75. DOI: 10.1039/b500852b. View

13.

Nevedomskaya E, Meissner A, Goraler S, de Waard M, Ridwan Y, Zondag G . Metabolic profiling of accelerated aging ERCC1 d/- mice. J Proteome Res. 2010; 9(7):3680-7. DOI: 10.1021/pr100210k. View

14.

Sanchon-Lopez B, Everett J . New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics: Topological Metabolite Identification Carbon Efficiency (tMICE). J Proteome Res. 2016; 15(9):3405-19. DOI: 10.1021/acs.jproteome.6b00631. View

15.

Novotny M, Jemiolo B, Wiesler D, Ma W, Harvey S, Xu F . A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice. Chem Biol. 1999; 6(6):377-83. DOI: 10.1016/S1074-5521(99)80049-0. View

16.

Liberles S . Mammalian pheromones. Annu Rev Physiol. 2013; 76:151-75. PMC: 4310675. DOI: 10.1146/annurev-physiol-021113-170334. View

17.

Faragher R . Should we treat aging as a disease? The consequences and dangers of miscategorisation. Front Genet. 2015; 6:171. PMC: 4500987. DOI: 10.3389/fgene.2015.00171. View

18.

Scott F, Gonzalez Malagon S, OBrien B, Fennema D, Veeravalli S, Coveney C . Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria. Drug Metab Dispos. 2017; 45(9):982-989. PMC: 5539585. DOI: 10.1124/dmd.117.076612. View

19.

Wishart D, Jewison T, Guo A, Wilson M, Knox C, Liu Y . HMDB 3.0--The Human Metabolome Database in 2013. Nucleic Acids Res. 2012; 41(Database issue):D801-7. PMC: 3531200. DOI: 10.1093/nar/gks1065. View

20.

Imai S . Dissecting systemic control of metabolism and aging in the NAD World: the importance of SIRT1 and NAMPT-mediated NAD biosynthesis. FEBS Lett. 2011; 585(11):1657-62. PMC: 3104082. DOI: 10.1016/j.febslet.2011.04.060. View