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Aging-related kidney damage is associated with a decrease in klotho expression and an increase in superoxide production

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Abstract

The purpose of this study was to determine changes in klotho, endothelin (ET) receptors, and superoxide production in kidneys of aged rats and whether these changes are exacerbated in aged rats with cognitive impairment. Twenty aged rats (male, 27 months) were divided into an Old Impaired group (n = 9) and an Old Intact group (n = 11) according to a cognitive function test. A group of 12-month-old rats (n = 10) was used as a Young Intact group. Serum creatinine was increased significantly in the Old Impaired group, suggesting impaired renal function. Aged rats showed glomerulosclerosis and tubulointerstitialfibrosis. These pathological changes were markedly aggravated in the old cognitively impaired than in the old cognitively intact animals. Notably, aged rats demonstrated a significant decrease in klotho protein expression in renal cortex and medulla. Protein expression of IL-6, Nox2, ETa receptors and superoxide production were increased whereas mitochondrial SOD (MnSOD) and ETb receptors expression were decreased in kidneys of the aged rats. Interestingly, these changes were more pronounced in the old impaired than in the old intact rats. In conclusion, the aging-related kidney damage was exacerbated in aged rats with cognitive impairment. Klotho, ETB, and MnSOD were downregulated but ETa, IL-6, Nox2, and superoxide production were upregulated in the aging-related kidney damage. These changes were more pronounced in rats with cognitive impairment.

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Acknowledgements

This work was supported by the National Institute of Health (R01 HL077490) and the Reynolds Oklahoma Center on Aging.

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Authors and Affiliations

  1. Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Xiuqing Wang, Yuhong Wang & Zhongjie Sun

  2. Department of Cardiology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China

    Zhong Zuo, Han Lei & Zhongjie Sun

  3. Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    William Sonntag

  4. The Robert and Mary Cade Laboratory, University of Oklahoma Health Sciences Center (OUHSC), 940 S. L. Young Blvd., Oklahoma City, OK, 73126-0901, USA

    Zhongjie Sun

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  1. Zhong Zuo
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  2. Han Lei
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  4. Yuhong Wang
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Correspondence to Zhongjie Sun.

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Zuo, Z., Lei, H., Wang, X. et al. Aging-related kidney damage is associated with a decrease in klotho expression and an increase in superoxide production. AGE 33, 261–274 (2011). https://doi.org/10.1007/s11357-010-9176-2

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  • DOI: https://doi.org/10.1007/s11357-010-9176-2

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