Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions

Abstract

Kidney fibrosis is the final common pathway of virtually all chronic kidney disease (CKD). However, despite great progress in recent years, no targeted antifibrotic therapies have been approved. Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of CKD. Senescent renal tubular cells, fibroblasts, endothelial cells, and podocytes have been detected in the kidneys of patients with CKD and animal models. Nonetheless, although accumulated evidence supports the essential role of cellular senescence in CKD, the mechanisms that promote cell senescence and how senescent cells contribute to CKD remain largely unknown. In this review, we summarize the features of the cellular senescence of the kidney and discuss the possible functions of senescent cells in the pathogenesis of kidney fibrosis. We also address whether pharmacological approaches targeting senescent cells can be used to retard the the progression of kidney fibrosis.

Keywords

cellular senescence / kidney fibrosis / cell cycle arrest / SASP / senolytics / senomorphics

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Acknowledgements

This work was supported by grants from National High Level Hospital Clinical Research Funding (Scientific Research Fund of Peking University First Hospital, No. 2023IR16; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, No. 24QZ003), the National Natural Science Foundation of China (Nos. 82090023 and 82330019) to Dr. Jing Nie; the grants from Science/Technology Project of Sichuan Province (No. 2024NSFSC1727) and the 1.3.5 project for disciplines of excellence from West China Hospital of Sichuan University (No. ZYGD23015) to Dr. Ping Fu.

Compliance with ethics guidelines

Conflicts of interest Lina Yang, Liang Ma, Ping Fu, and Jing Nie declare no competing interests.

This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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