Renal inflammation combined with renal function reserve reduction accelerate kidney aging via pentose phosphate pathway

肾脏炎症联合肾功能储备降低通过磷酸戊糖途径加速肾脏衰老

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作者:Bing Han, YiXuan Zhang, Chao Liu, Pengcheng Ji, Zenghui Xing, Xiaodong Geng, Kun Chi, Ming Gong, Yingying Li, Ying Zhang, Zhangning Fu, Quan Hong, Guangyan Cai, Xiangmei Chen, Xuefeng Sun

Abstract

Aging is closely associated with inflammation, which affects renal function reserve (RFR) in the kidneys. This study aims to investigate the impact of reduced RFR reduction on kidney aging and the influence of renal inflammation and RFR reduction on this process. Natural aging rats and those subjected to unilateral nephrectomy (UNX), 1/6 nephrectomy (1/6NX), and unilateral ureteral obstruction (UUO) were observed at 6, 12, 18, and 21 months. Our findings suggest that RFR reduction and renal inflammation can accelerate kidney aging, and inflammation contributes more. Metabolomics analysis revealed alterations in amino acid metabolism contribute to RFR decline. Furthermore, experiments in vitro confirmed the involvement of pentose phosphate pathway (PPP) in promoting aging though inflammation. Our research provides novel insights into for the mechanism of kidney aging and provides indirect support for clinical treatment decisions, such as addressing kidney inflammation, stones, or tumors that may necessitate partial or complete nephrectomy.

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