Korean J Med.
2017 Feb;92(1):53-61. 10.3904/kjm.2017.92.1.53.
Age-related Changes in the Sirtuin1-NFE2-related Factor 2 Signaling System in the Kidney
- Affiliations
-
- 1Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. sooncb@catholic.ac.kr
- 2Department of Internal Medicine, The Catholic University of Korea Seoul St. Mary's Hospital, Seoul, Korea.
- 3Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
- 4Department of Internal Medicine, The Catholic University of Korea Yeouido St. Mary's Hospital, Seoul, Korea.
- KMID: 2376944
- DOI: http://doi.org/10.3904/kjm.2017.92.1.53
Abstract
- BACKGROUND/AIMS
Renal aging-related changes are characterized by oxidative stress. SIRT1 regulates cellular conditions by activating Nrf2. The present study investigated the processes of renal changes by antioxidant enzymes and the relationship between SIRT1 and Nrf2.
METHODS
We used male 2-, 12-, and 24-month-old C57BL/6 mice. We measured renal function, histological changes, oxidative stress, and expression of SIRT1-Nrf2 signaling in the kidneys.
RESULTS
24-month-old mice exhibited increased albuminuria and serum creatinine. Creatinine clearance was decreased in 24-month-old mice compared with 12-month-old mice. There were increases in mesangial volume and tubulointerstitial fibrosis in 24-month-old mice. Moreover, oxidative stress marker, 3-Nitrotyrosine, expression and apoptosis were increased in 24-month-old mice. The 24 h urinary 8-isoprostane and 8-hydroxy-deoxyguanosine excretion increased with aging. The levels of expression of SIRT1 and nuclear Nrf2 were decreased in 24-month-old mice. The antioxidant enzymes HO-1 and NQO-1 were down-regulated in 24-month-old mice. Another antioxidant enzyme, SOD2, was decreased in 24-month-old mice.
CONCLUSIONS
Our results demonstrated that SIRT1 was down-regulated with aging, and this may be related to changes in the expression of target molecules including Nrf2. As a result, oxidative stress was induced. The pharmacological targeting of these signaling molecules may reduce the pathological changes associated with aging in the kidney.
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