Cellular senescence in renal ischemia-reperfusion injury.

IF 7.3 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Ying Chen, Li Yang
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Abstract

Abstract: Acute kidney injury (AKI) affects more than 20% of hospitalized patients and is a significant contributor to morbidity and mortality, primarily due to ischemia/reperfusion injury (IRI), which is one of the leading causes of AKI. IRI not only exacerbates the immediate impact of AKI but also facilitates its progression to chronic kidney disease (CKD) and, in cases of preexisting CKD, to end-stage renal disease (ESRD). One of the critical pathological processes associated with IRI-AKI is cellular senescence, characterized by an irreversible arrest in the cell cycle, morphological and chromatin organization changes, altered transcriptional and metabolic profiles, and the development of a hypersecretory phenotype known as the senescence-associated secretory phenotype (SASP). The SASP amplifies senescence signals in surrounding normal cells through senescence-related pathways, contributing to tissue damage, fibrosis, and chronic inflammation. This review provides an overview of the defining features of senescent cells and explores the fundamental mechanisms underlying senescent cell generation following IRI. We elucidate the pivotal roles of cellular senescence in the transition from IRI-AKI to chronic kidney injury. Furthermore, we discuss emerging therapies targeting cellular senescence, including senolytics and senomorphics, which have shown promising results in both preclinical and clinical settings. These therapies position cellular senescence as a crucial target for the treatment of IRI in the kidneys. Additionally, advancements in single-cell sequencing technology and artificial intelligence-assisted drug screening are expected to accelerate the discovery of novel senescent biomarkers and synotherapeutics, paving the way for optimized and personalized therapeutic interventions.

肾缺血再灌注损伤中的细胞衰老。
急性肾损伤(AKI)影响了超过20%的住院患者,是发病率和死亡率的重要因素,主要是由于缺血/再灌注损伤(IRI),这是AKI的主要原因之一。IRI不仅会加剧AKI的直接影响,还会促进其发展为慢性肾脏疾病(CKD),并且在先前存在CKD的情况下,会发展为终末期肾脏疾病(ESRD)。与IRI-AKI相关的关键病理过程之一是细胞衰老,其特征是细胞周期的不可逆停滞,形态和染色质组织的改变,转录和代谢谱的改变,以及称为衰老相关分泌表型(SASP)的高分泌表型的发展。SASP通过衰老相关途径放大周围正常细胞的衰老信号,导致组织损伤、纤维化和慢性炎症。本文综述了衰老细胞的定义特征,并探讨了IRI后衰老细胞产生的基本机制。我们阐明了细胞衰老在IRI-AKI向慢性肾损伤转变中的关键作用。此外,我们还讨论了针对细胞衰老的新兴疗法,包括抗衰老药物和senolytics,这些疗法在临床前和临床环境中都显示出有希望的结果。这些疗法将细胞衰老定位为肾脏IRI治疗的关键靶点。此外,单细胞测序技术和人工智能辅助药物筛选的进步有望加速发现新的衰老生物标志物和关节疗法,为优化和个性化的治疗干预铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Chinese Medical Journal
Chinese Medical Journal 医学-医学:内科
CiteScore
9.80
自引率
4.90%
发文量
19245
审稿时长
6 months
期刊介绍: The Chinese Medical Journal (CMJ) is published semimonthly in English by the Chinese Medical Association, and is a peer reviewed general medical journal for all doctors, researchers, and health workers regardless of their medical specialty or type of employment. Established in 1887, it is the oldest medical periodical in China and is distributed worldwide. The journal functions as a window into China’s medical sciences and reflects the advances and progress in China’s medical sciences and technology. It serves the objective of international academic exchange. The journal includes Original Articles, Editorial, Review Articles, Medical Progress, Brief Reports, Case Reports, Viewpoint, Clinical Exchange, Letter,and News,etc. CMJ is abstracted or indexed in many databases including Biological Abstracts, Chemical Abstracts, Index Medicus/Medline, Science Citation Index (SCI), Current Contents, Cancerlit, Health Plan & Administration, Embase, Social Scisearch, Aidsline, Toxline, Biocommercial Abstracts, Arts and Humanities Search, Nuclear Science Abstracts, Water Resources Abstracts, Cab Abstracts, Occupation Safety & Health, etc. In 2007, the impact factor of the journal by SCI is 0.636, and the total citation is 2315.
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