Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis

Kidney dysfunction is particularly important in systemic organ injuries caused by aging. Metabolomics are utilized in this study to explore the mechanism of kidney dysfunction during aging by the identification of metabolites and the characterization of metabolic pathways. We analyzed the serum bioc...

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Main Authors: Danli Jiao, Li Qi, Li Hu, Dan Hu, Xiao Li, Guona Li, Zheying Li, Shimin Liu, Chen Zhao, Huangan Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.959311/full
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author Danli Jiao
Li Qi
Li Hu
Dan Hu
Xiao Li
Guona Li
Guona Li
Zheying Li
Shimin Liu
Chen Zhao
Huangan Wu
author_facet Danli Jiao
Li Qi
Li Hu
Dan Hu
Xiao Li
Guona Li
Guona Li
Zheying Li
Shimin Liu
Chen Zhao
Huangan Wu
author_sort Danli Jiao
collection DOAJ
description Kidney dysfunction is particularly important in systemic organ injuries caused by aging. Metabolomics are utilized in this study to explore the mechanism of kidney dysfunction during aging by the identification of metabolites and the characterization of metabolic pathways. We analyzed the serum biochemistry and kidney histopathology of male Kunming mice aged 3 months and 24 months and found that the aged mice had inflammatory lesions, aggravated fibrosis, and functional impairment. A high-resolution untargeted metabolomics analysis revealed that the endogenous metabolites in the kidneys and urine of the mice were significantly changed by 25 and 20 metabolites, respectively. A pathway analysis of these differential metabolites revealed six key signaling pathways, namely, D-glutamine and D-glutamate metabolism, purine metabolism, the citrate cycle [tricarboxylic acid (TCA) cycle], histidine metabolism, pyruvate metabolism, and glyoxylate and dicarboxylate metabolism. These pathways are involved in amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism, and these can lead to immune regulation, inflammatory responses, oxidative stress damage, cellular dysfunction, and bioenergy disorders, and they are closely associated with aging and kidney insufficiency. We also screened nine types of sensitive metabolites in the urine as potential biomarkers of kidney dysfunction during the aging process to confirm their therapeutic targets in senior-induced kidney dysfunction and to improve the level of risk assessment for senile kidney injury.
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spelling doaj.art-fc20dd4a6bda4bda92c627b8748bfdf52022-12-22T03:11:59ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-09-011310.3389/fendo.2022.959311959311Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysisDanli Jiao0Li Qi1Li Hu2Dan Hu3Xiao Li4Guona Li5Guona Li6Zheying Li7Shimin Liu8Chen Zhao9Huangan Wu10School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKidney dysfunction is particularly important in systemic organ injuries caused by aging. Metabolomics are utilized in this study to explore the mechanism of kidney dysfunction during aging by the identification of metabolites and the characterization of metabolic pathways. We analyzed the serum biochemistry and kidney histopathology of male Kunming mice aged 3 months and 24 months and found that the aged mice had inflammatory lesions, aggravated fibrosis, and functional impairment. A high-resolution untargeted metabolomics analysis revealed that the endogenous metabolites in the kidneys and urine of the mice were significantly changed by 25 and 20 metabolites, respectively. A pathway analysis of these differential metabolites revealed six key signaling pathways, namely, D-glutamine and D-glutamate metabolism, purine metabolism, the citrate cycle [tricarboxylic acid (TCA) cycle], histidine metabolism, pyruvate metabolism, and glyoxylate and dicarboxylate metabolism. These pathways are involved in amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism, and these can lead to immune regulation, inflammatory responses, oxidative stress damage, cellular dysfunction, and bioenergy disorders, and they are closely associated with aging and kidney insufficiency. We also screened nine types of sensitive metabolites in the urine as potential biomarkers of kidney dysfunction during the aging process to confirm their therapeutic targets in senior-induced kidney dysfunction and to improve the level of risk assessment for senile kidney injury.https://www.frontiersin.org/articles/10.3389/fendo.2022.959311/fullnatural agingkidney dysfunctionuntargeted metabolomicsurinebiomarkers
spellingShingle Danli Jiao
Li Qi
Li Hu
Dan Hu
Xiao Li
Guona Li
Guona Li
Zheying Li
Shimin Liu
Chen Zhao
Huangan Wu
Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis
Frontiers in Endocrinology
natural aging
kidney dysfunction
untargeted metabolomics
urine
biomarkers
title Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis
title_full Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis
title_fullStr Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis
title_full_unstemmed Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis
title_short Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis
title_sort changes in aging induced kidney dysfunction in mice based on a metabolomics analysis
topic natural aging
kidney dysfunction
untargeted metabolomics
urine
biomarkers
url https://www.frontiersin.org/articles/10.3389/fendo.2022.959311/full
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