Goyal Kavita, Afzal Muhammad, Altamimi Abdulmalik Saleh Alfawaz, Babu M Arockia, Ballal Suhas, Kaur Irwanjot, Kumar Sachin, Kumar M Ravi, Chauhan Ashish Singh, Ali Haider, Shahwan Moyad, Gupta Gaurav
Department of Biotechnology, Graphic Era (Deemed to Be University), Clement Town, Dehradun, 248002, India.
Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, 21442, Jeddah, Saudi Arabia.
Biogerontology. 2024 Dec 26;26(1):32. doi: 10.1007/s10522-024-10173-z.
Chronic kidney diseases (CKD) are a group of multi-factorial disorders that markedly impair kidney functions with progressive renal deterioration. Aging contributes to age-specific phenotypes in kidneys, which undergo several structural and functional alterations, such as a decline in regenerative capacity and increased fibrosis, inflammation, and tubular atrophy, all predisposing them to disease and increasing their susceptibility to injury while impeding their recovery. A central feature of these age-related processes is the activation of the p53/p21 pathway signaling. The pathway is a key player in cellular senescence, apoptosis, and cell cycle regulation, which are all key to maintaining the health of the kidney. P53 is a transcription factor and a tumor suppressor protein that responds to cell stress and damage. Persistent activation of cell p53 can lead to the expression of p21, an inhibitor of the cell cycle known as a cyclin-dependent kinase. This causes cells to cease dividing and leads to senescence, where cells can no longer increase. The accumulation of senescent cells in the aging kidney impairs kidney function by altering the microenvironment. As the number of senescent cells increases, the capacity of the kidney to recover from injury decreases, accelerating the progression of end-stage renal disease. This article review extensively explores the relationship between the p53/p21 pathway and cellular senescence within an aging kidney and the emerging therapeutic strategies that target it to overcome the impacts of cellular senescence on CKD.
慢性肾脏病（CKD）是一组多因素疾病，会随着肾脏功能的逐渐恶化而显著损害肾功能。衰老导致肾脏出现特定年龄阶段的表型变化，肾脏会经历一些结构和功能改变，比如再生能力下降、纤维化增加、炎症反应以及肾小管萎缩，所有这些都使肾脏易患疾病，增加其对损伤的易感性，同时阻碍其恢复。这些与年龄相关过程的一个核心特征是p53/p21信号通路的激活。该通路在细胞衰老、凋亡和细胞周期调控中起关键作用，而这些对于维持肾脏健康都至关重要。P53是一种转录因子和肿瘤抑制蛋白，对细胞应激和损伤作出反应。细胞p53的持续激活会导致p21的表达，p21是一种细胞周期抑制剂，被称为细胞周期蛋白依赖性激酶。这会导致细胞停止分裂并进入衰老状态，此时细胞不再增殖。衰老细胞在衰老肾脏中的积累会通过改变微环境来损害肾功能。随着衰老细胞数量的增加，肾脏从损伤中恢复的能力下降，加速了终末期肾病的进展。本文广泛探讨了衰老肾脏中p53/p21通路与细胞衰老之间的关系，以及针对该通路以克服细胞衰老对慢性肾脏病影响的新兴治疗策略。
