Age-related Changes in the Sirtuin1-NFE2-related Factor 2 Signaling System in the Kidney.
- Author:
Myoung Nam BAE
1
;
Min Seok CHOI
;
Sang hoon EUM
;
Eun Nim KIM
;
Ji Hee LIM
;
Min Young KIM
;
Tae Hyun BAN
;
In Ae JANG
;
Hye Eun YOON
;
Cheol Whee PARK
;
Yoon Sik CHANG
;
Bum Soon CHOI
Author Information
- Publication Type:Original Article
- Keywords: Aging; Kidney; NF-E2-Related Factor 2; Oxidative stress; Sirtuin 1
- MeSH: Aging; Albuminuria; Animals; Apoptosis; Child, Preschool; Creatinine; Fibrosis; Humans; Infant; Kidney*; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Sirtuin 1
- From:Korean Journal of Medicine 2017;92(1):53-61
- CountryRepublic of Korea
- Language:English
- 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.
