Ma Si-Jia, Zhu Yu-Ting, He Fang-Fang, Zhang Chun
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int J Mol Sci. 2025 Sep 19;26(18):9159. doi: 10.3390/ijms26189159.
Podocytes are highly specialized, terminally differentiated epithelial cells essential for maintaining the glomerular filtration barrier. Their limited regenerative capacity and high metabolic demands render them particularly susceptible to aging-related stress. Accumulating evidence indicates that podocyte aging, characterized by cellular senescence, mitochondrial dysfunction, autophagy impairment, and epigenetic alterations, significantly contributes to the pathogenesis of diverse glomerular diseases collectively termed podocytopathies. These include focal segmental glomerulosclerosis, membranous nephropathy, minimal change disease, diabetic kidney disease, and lupus nephritis. This review discusses the cellular and molecular mechanisms driving podocyte aging and explores how these alterations predispose to podocyte injury, loss, and dysfunction, ultimately culminating in podocytopathies. Furthermore, we highlight current and emerging therapeutic strategies that aim to preserve podocyte health by targeting aging-associated pathways. Understanding podocyte aging elucidates mechanisms of chronic kidney disease progression and identifies novel therapeutic strategies for age-specific interventions in podocytopathies.
足细胞是高度特化的终末分化上皮细胞，对维持肾小球滤过屏障至关重要。它们有限的再生能力和高代谢需求使它们特别容易受到与衰老相关的应激影响。越来越多的证据表明，以细胞衰老、线粒体功能障碍、自噬受损和表观遗传改变为特征的足细胞衰老，显著促成了统称为足细胞病的多种肾小球疾病的发病机制。这些疾病包括局灶节段性肾小球硬化、膜性肾病、微小病变肾病、糖尿病肾病和狼疮性肾炎。本综述讨论了驱动足细胞衰老的细胞和分子机制，并探讨了这些改变如何导致足细胞损伤、丢失和功能障碍，最终导致足细胞病。此外，我们强调了当前和新兴的治疗策略，这些策略旨在通过靶向与衰老相关的途径来维持足细胞健康。了解足细胞衰老阐明了慢性肾脏病进展的机制，并确定了针对足细胞病进行年龄特异性干预的新治疗策略。
