Research Paper Volume 13, Issue 17 pp 21009—21028
Glutathione is an aging-related metabolic signature in the mouse kidney
- 1 Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seodaemun-Gu, Seoul 03759, Korea
- 2 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-Gu, Daejeon 34141, Korea
- 3 Aventi Inc., Yuseong-Gu, Daejeon 34141, Korea
- 4 Department of Chemistry and Nano Science, Ewha Womans University, Seodaemun-Gu, Seoul 03760, Korea
Received: July 12, 2021 Accepted: August 24, 2021 Published: September 7, 2021https://doi.org/10.18632/aging.203509
How to Cite
Copyright: © 2021 Ahn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 by data 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 immune-related 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.