Injury in nonaged podocytes as an accelerator of glomerular aging.
Injury in nonaged podocytes as an accelerator of glomerular aging.
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非衰老足细胞损伤是肾小球衰老的加速器。
DOI：
10.1152/ajprenal.00344.2023
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
He,JohnCijiang
中科院分区：
文献类型：
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作者：
Fang,Zhengying;Lee,Kyung;He,JohnCijiang
7 随着全球老龄化人口的增加，与老龄化相关的疾病 8 日益受到关注。众所周知，衰老会对肾脏健康产生负面影响，因为肾单位 9 数量减少，肾小球滤过率下降。年龄依赖性肾小球硬化症 10 是与年龄相关的肾脏变化的一个特征，是由于肾小球驻留细胞（包括足细胞）数量和功能减少所致 11 。足细胞是终末分化的 12 肾小球上皮细胞，其覆盖下面的肾小球基底膜以 13 维持适当的肾小球滤过。由于足细胞是不可再生的细胞，提高 14 足细胞的健康寿命和减少足细胞的损失非常重要。通过评估老年大鼠的肾脏 15 变化，Floege 等人在 25 多年前首次报告足细胞在 16 与年龄相关的肾小球硬化症中发挥着核心作用 1。人类研究还强调 17 足细胞是受衰老影响的关键细胞类型，因为在没有明显肾脏疾病的个体中，老年独立地导致 18 足细胞耗竭 2, 3. 19 20 有趣的是，在衰老肾脏中观察到的足细胞密度降低同样发生在 21 患有肾小球疾病的年轻患者的肾脏中，这表明与年龄相关的 22 肾小球硬化症与肾小球疾病诱发的 23 肾小球硬化症 2 具有相似的病理事件。此外，不断积累的研究表明，足细胞衰老和 24 肾小球疾病相关的足细胞损伤具有一些共同的细胞和分子变化，25包括 mTOR/AMPK 信号通路 4、5 的过度激活和 Sirtuin 失调 6、7。26 这些证据提供了部分线索，说明为什么老年患者更容易患相同的 27 肾小球疾病，并且往往比年轻患者的预后更差。然而，28 疾病引起的足细胞损伤和衰老引起的足细胞损伤之间的交叉点尚未得到充分探索 29，因此足细胞损伤是否加速肾小球衰老仍不清楚 30。 31
7 With the increase in the aging population worldwide, diseases associated with aging are of 8 increasing concern. It is known that aging negatively affects kidney health, as the nephron 9 number decreases and the glomerular filtration rate declines. Age-dependent glomerulosclerosis 10 is a characteristic of age-associated kidney changes, resulting from reduced number and function 11 of glomerular resident cells, including podocytes. Podocytes are terminally differentiated 12 glomerular epithelial cells, which cover the underlying glomerular basement membrane to 13 maintain proper glomerular filtration. As podocytes are non-regenerative cells, enhancing 14 podocyte health span and reducing podocyte loss is of great importance. By assessing renal 15 changes in aged rats, Floege et al., were the first to report that podocyte plays a central role in 16 age-associated glomerulosclerosis, more than 25 years ago 1. Human studies also underscore 17 podocyte as a critical cell type affected by aging, as older age independently contributes to 18 podocyte depletion in individuals without overt renal disease 2, 3. 19 20Intriguingly, the reduction in podocyte density observed in aging kidneys similarly took place in 21 the kidneys of young patients with glomerular diseases, indicating that age-related 22 glomerulosclerosis shares similar pathologic events with glomerular disease-induced 23 glomerulosclerosis 2. Moreover, accumulating studies have shown that podocyte aging and 24 glomerular disease-associated podocyte injury have some shared cellular and molecular changes, 25 including hyperactivation of mTOR/AMPK signaling pathway 4, 5 and sirtuin dysregulation 6, 7. 26 Such evidence provides partial clues as to why older patients are more susceptible to the same 27 glomerular disease and tend to have poorer prognoses than young patients. However, the 28 intersection between disease-induced and aging-induced podocyte injury has not been 29 sufficiently explored, and thus whether podocyte injury accelerates glomerular aging remains 30 unclear. 31