作为肾小球滤过膜的重要组成部分,足细胞的状态与肾功能密切相关,它们也是参与衰老的关键细胞,在肾脏衰老引起的损害中起着核心作用。因此,了解足细胞的衰老过程将使我们了解其对损伤的敏感性并确定有针对性的保护机制。事实上,生理衰老过程本身可以诱导足细胞衰老。病理性应激,如氧化应激,线粒体损伤,衰老相关分泌表型的分泌,减少自噬,癌基因激活,改变的转录因子,DNA损伤反应,和其他因素,在诱导早衰和加速衰老中起着至关重要的作用。衰老相关β-半乳糖苷酶(SA-β-gal)是衰老的标志,β-羟基丁酸处理可降低SA-β-gal活性,减轻细胞衰老和损伤。此外,CCAAT/增强子结合蛋白-α,转化生长因子-β信号传导,糖原合成酶激酶-3β,周期依赖性激酶,程序性细胞死亡蛋白1和纤溶酶原激活物抑制剂1与衰老密切相关。这些因素的缺乏或升高可以通过不同的机制影响衰老。足细胞损伤不是一个独立的过程,损伤的足细胞与周围上皮细胞或其他肾细胞相互作用,介导足细胞的损伤或损失。在这次审查中,我们讨论的表现,分子机制,生物标志物,和足细胞衰老的治疗药物。我们包括了埃拉米肽,锂,卡路里限制,雷帕霉素;和新兴的治疗策略,如基因和免疫疗法。更重要的是,我们总结了足细胞如何与其他肾细胞相互作用。
As an important component of the glomerular filtration membrane, the state of the
podocytes is closely related to kidney function, they are also key cells involved in aging and play a central role in the damage caused by renal aging. Therefore, understanding the aging process of
podocytes will allow us to understand their susceptibility to injury and identify targeted protective mechanisms. In fact, the process of physiological aging itself can induce podocyte senescence. Pathological stresses, such as oxidative stress, mitochondrial damage, secretion of senescence-associated secretory phenotype, reduced autophagy, oncogene activation, altered transcription factors, DNA damage response, and other factors, play a crucial role in inducing premature senescence and accelerating aging. Senescence-associated-β-galactosidase (SA-β-gal) is a marker of aging, and β-hydroxybutyric acid treatment can reduce SA-β-gal activity to alleviate cellular senescence and damage. In addition, CCAAT/enhancer-binding protein-α, transforming growth factor-β signaling, glycogen synthase kinase-3β, cycle-dependent kinase, programmed cell death protein 1, and plasminogen activator inhibitor-1 are closely related to aging. The absence or elevation of these factors can affect aging through different mechanisms. Podocyte injury is not an independent process, and injured
podocytes interact with the surrounding epithelial cells or other kidney cells to mediate the injury or loss of
podocytes. In this review, we discuss the manifestations, molecular mechanisms, biomarkers, and therapeutic drugs for podocyte senescence. We included elamipretide, lithium, calorie restriction, rapamycin; and emerging treatment strategies, such as gene and immune therapies. More importantly, we summarize how podocyte interact with other kidney cells.