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C57BL/6J野生型和含黄素单加氧酶5（FMO5）基因敲除小鼠衰老的代谢生物标志物

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

作者信息

Varshavi Dorsa, Scott Flora H, Varshavi Dorna, Veeravalli Sunil, Phillips Ian R, Veselkov Kirill, Strittmatter Nicole, Takats Zoltan, Shephard Elizabeth A, Everett Jeremy R

机构信息

Medway Metabonomics Research Group, University of Greenwich, Chatham, United Kingdom.

Institute of Structural and Molecular Biology, University College London, London, United Kingdom.

出版信息

Front Mol Biosci. 2018 Apr 9;5:28. doi: 10.3389/fmolb.2018.00028. eCollection 2018.

DOI:10.3389/fmolb.2018.00028
PMID:29686991
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5900034/
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.

摘要

最近在小鼠中证实，敲除含黄素单加氧酶5基因（FMO5）可通过多效性作用减缓代谢衰老。我们现在使用基于核磁共振的代谢组学方法，直接研究衰老对回交到C57BL/6J背景的雄性野生型C57BL/6J和FMO5基因敲除（FMO5 KO）小鼠尿液和血浆代谢谱的影响。本研究的目的是确定这两种小鼠品系中与衰老相关的代谢特征，并在相同时间点表征FMO5 KO小鼠与其野生型对照之间代谢物谱的年龄相关差异。我们在尿液和血浆中都鉴定出了一系列与年龄相关的生物标志物。一些代谢物，包括尿液中的6-羟基-6-甲基庚-3-酮（6H6MH3O），一种小鼠性信息素，无论基因背景如何，都显示出随年龄变化的相似模式。然而，其他一些代谢物仅在FMO5 KO小鼠中发生改变，或仅在野生型小鼠中发生改变，这表明基因修饰对小鼠衰老的影响。尿液中牛磺酸浓度升高是仅在野生型小鼠中观察到的一种独特的、与衰老相关的变化。

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