To target cellular senescence in diabetic kidney disease: the known and the unknown

Author:

Wei Yuehan12,Mou Shan2,Yang Qing3,Liu Fang3ORCID,Cooper Mark E.1,Chai Zhonglin1ORCID

Affiliation:

1. 1Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Australia

2. 2Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Ren Ji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

3. 3Department of Nephrology, Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, China

Abstract

Abstract Cellular senescence represents a condition of irreversible cell cycle arrest, characterized by heightened senescence-associated beta-galactosidase (SA-β-Gal) activity, senescence-associated secretory phenotype (SASP), and activation of the DNA damage response (DDR). Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease (ESRD) globally, with ongoing unmet needs in terms of current treatments. The role of senescence in the pathogenesis of DKD has attracted substantial attention with evidence of premature senescence in this condition. The process of cellular senescence in DKD appears to be associated with mitochondrial redox pathways, autophagy, and endoplasmic reticulum (ER) stress. Increasing accumulation of senescent cells in the diabetic kidney not only leads to an impaired capacity for repair of renal injury, but also the secretion of pro-inflammatory and profibrotic cytokines and growth factors causing inflammation and fibrosis. Current treatments for diabetes exhibit varying degrees of renoprotection, potentially via mitigation of senescence in the diabetic kidney. Targeting senescent cell clearance through pharmaceutical interventions could emerge as a promising strategy for preventing and treating DKD. In this paper, we review the current understanding of senescence in DKD and summarize the possible therapeutic interventions relevant to senescence in this field.

Funder

National Health and Medical Research Council

Publisher

Portland Press Ltd.

Reference175 articles.

1. Senescence and rejuvenation;Minot;J. Physiol.,1891

2. The serial cultivation of human diploid cell strains;Hayflick;Exp. Cell. Res.,1961

3. Forging a signature of in vivo senescence;Sharpless;Nat. Rev. Cancer,2015

4. Cellular senescence: aging, cancer, and injury;Calcinotto;Physiol. Rev.,2019

5. Hallmarks of cellular senescence;Hernandez-Segura;Trends Cell Biol.,2018

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3