Glutathione is an aging-related metabolic signature in the mouse kidney

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Title
Glutathione is an aging-related metabolic signature in the mouse kidney
Author(s)
E Ahn; J Lee; J Han; Seung-Min LeeKi-Sun Kwon; G S Hwang
Bibliographic Citation
Aging-US, vol. 13, no. 17, pp. 21009-21028
Publication Year
2021
Abstract
The ability to maintain systemic metabolic homeostasis through various mechanisms represents a crucial strength of kidneys in the study of metabolic syndrome or aging. Moreover, age-associated kidney failure has been widely accepted. However, efforts to demonstrate aging-dependent renal metabolic rewiring have been limited. In the present study, we investigated aging-related renal metabolic determinants by integrating metabolomic and transcriptomic data sets from kidneys of young (3 months, n = 7 and 3 for respectively) and old (24 months, n = 8 and 3 for respectively) naive C57BL/6 male mice. Metabolite profiling analysis was conducted, followed bydata processing via network and pathway analyses, to identify differential metabolites. In the aged group, the levels of glutathione and oxidized glutathione were significantly increased, but the levels of gamma-glutamyl amino acids, amino acids combined with the gamma-glutamyl moiety from glutathione by membrane transpeptidases, and circulating glutathione levels were decreased. In transcriptomic analysis, differential expression of metabolic enzymes is consistent with the hypothesis of aging-dependent rewiring in renal glutathione metabolism; pathway and network analyses further revealed the increased expression of immunerelated genes in the aged group. Collectively, our integrative analysis results revealed that defective renal glutathione metabolism is a signature of renal aging. Therefore, we hypothesize that restraining renal glutathione metabolism might alleviate or delay age-associated renal metabolic deterioration, and aberrant activation of the renal immune system.
Keyword
Glutathione metabolismMetabolomicsTranscriptomicsRenal aging
ISSN
1945-4589
Publisher
Impact Journals Llc
DOI
http://dx.doi.org/10.18632/aging.203509
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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