Pathological mechanisms of kidney disease in ageing

IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Nature Reviews Nephrology Pub Date : 2024-07-18 DOI:10.1038/s41581-024-00868-4
Takeshi Yamamoto, Yoshitaka Isaka
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Abstract

The kidney is a metabolically active organ that requires energy to drive processes such as tubular reabsorption and secretion, and shows a decline in function with advancing age. Various molecular mechanisms, including genomic instability, telomere attrition, inflammation, autophagy, mitochondrial function, and changes to the sirtuin and Klotho signalling pathways, are recognized regulators of individual lifespan and pivotal factors that govern kidney ageing. Thus, mechanisms that contribute to ageing not only dictate renal outcomes but also exert a substantial influence over life expectancy. Conversely, kidney dysfunction, in the context of chronic kidney disease (CKD), precipitates an expedited ageing trajectory in individuals, leading to premature ageing and a disconnect between biological and chronological age. As CKD advances, age-related manifestations such as frailty become increasingly conspicuous. Hence, the pursuit of healthy ageing necessitates not only the management of age-related complications but also a comprehensive understanding of the processes and markers that underlie systemic ageing. Here, we examine the hallmarks of ageing, focusing on the mechanisms by which they affect kidney health and contribute to premature organ ageing. We also review diagnostic methodologies and interventions for premature ageing, with special consideration given to the potential of emerging therapeutic avenues to target age-related kidney diseases. The ability of the kidney to function normally declines with advancing age. This Review describes ageing processes that are relevant to age-related kidney diseases and the pathological mechanisms of chronic kidney disease in the context of premature ageing, as well as implications for diagnostic and therapeutic interventions.

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老龄化肾病的病理机制。
肾脏是一个新陈代谢活跃的器官,需要能量来驱动肾小管重吸收和分泌等过程,随着年龄的增长,肾脏的功能也会下降。各种分子机制,包括基因组不稳定性、端粒损耗、炎症、自噬、线粒体功能以及 sirtuin 和 Klotho 信号通路的变化,都是公认的个体寿命调节因素和肾脏老化的关键因素。因此,导致衰老的机制不仅决定了肾脏的预后,还对预期寿命产生了重大影响。相反,慢性肾脏病(CKD)中的肾功能障碍会加速个体的衰老轨迹,导致过早衰老以及生理年龄与实际年龄的脱节。随着 CKD 病程的延长,衰弱等与年龄相关的表现越来越明显。因此,要追求健康的老龄化,不仅需要控制与年龄相关的并发症,还需要全面了解导致系统老化的过程和标志物。在此,我们研究了衰老的标志,重点是它们影响肾脏健康和导致器官过早衰老的机制。我们还回顾了早衰的诊断方法和干预措施,并特别考虑了针对老年相关肾脏疾病的新兴治疗途径的潜力。
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来源期刊
Nature Reviews Nephrology
Nature Reviews Nephrology 医学-泌尿学与肾脏学
CiteScore
39.00
自引率
1.20%
发文量
127
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Nephrology aims to be the premier source of reviews and commentaries for the scientific communities it serves. It strives to publish authoritative, accessible articles. Articles are enhanced with clearly understandable figures, tables, and other display items. Nature Reviews Nephrology publishes Research Highlights, News & Views, Comments, Reviews, Perspectives, and Consensus Statements. The content is relevant to nephrologists and basic science researchers. The broad scope of the journal ensures that the work reaches the widest possible audience.
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