Podocyte mPGES-2 Determines Renal Aging and Contributes to Senile Osteoporosis.

Dandan Zhong, Chang Hao, Mengyue Li, Jing Liu, Zheng Xu, Jianteng Zhou, Lu Zhao, Siyu Ni, Zhenchao Hu, Yue Sun, Yingying Zou, Dong Sun, Hao Guo, Zhanjun Jia, Dong Guo, Jun-Li Cao, Ying Sun

Jiangsu Key Laboratory of Geriatric Precision Medicine and Aging Intervention, Xuzhou Medical University, Xuzhou, Jiangsu, China.Jiangsu Key Laboratory of Geriatric Precision Medicine and Aging Intervention, Xuzhou Medical University, Xuzhou, Jiangsu, China. · pubmed

Paper

Abstract

Renal aging shortens healthspan and propagates organ dysfunction beyond the kidney, yet its molecular drivers remain incompletely defined. Here we identify microsomal prostaglandin E synthase-2 (mPGES-2) as a critical regulator of renal aging and its skeletal consequence. Genetic ablation of Ptges2 improved health indices in aged mice, prolonged median survival, and markedly alleviated glomerulosclerosis, podocyte injury, and renal senescence. Single-cell transcriptomic analysis, together with podocyte- and tubule-specific knockout models, showed that podocyte mPGES-2, rather than tubular mPGES-2, is the dominant intrarenal driver of aging-related kidney injury. Mechanistically, mPGES-2 promoted podocyte senescence through a PGE

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Research summary

Podocyte-specific deletion of mPGES-2 mitigates renal aging and extends healthspan in mice by reducing senescence and glomerulosclerosis. This work identifies a specific molecular driver of organ-level aging that, when targeted, improves systemic health metrics, offering a potential therapeutic avenue for age-related renal decline.

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