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Cellular senescence: the good, the bad and the unknown
Nature Reviews Nephrology ( IF 28.6 ) Pub Date : 2022-08-03 , DOI: 10.1038/s41581-022-00601-z
Weijun Huang 1, 2 , LaTonya J Hickson 3 , Alfonso Eirin 1 , James L Kirkland 4 , Lilach O Lerman 1
Affiliation  

Cellular senescence is a ubiquitous process with roles in tissue remodelling, including wound repair and embryogenesis. However, prolonged senescence can be maladaptive, leading to cancer development and age-related diseases. Cellular senescence involves cell-cycle arrest and the release of inflammatory cytokines with autocrine, paracrine and endocrine activities. Senescent cells also exhibit morphological alterations, including flattened cell bodies, vacuolization and granularity in the cytoplasm and abnormal organelles. Several biomarkers of cellular senescence have been identified, including SA-βgal, p16 and p21; however, few markers have high sensitivity and specificity. In addition to driving ageing, senescence of immune and parenchymal cells contributes to the development of a variety of diseases and metabolic disorders. In the kidney, senescence might have beneficial roles during development and recovery from injury, but can also contribute to the progression of acute kidney injury and chronic kidney disease. Therapies that target senescence, including senolytic and senomorphic drugs, stem cell therapies and other interventions, have been shown to extend lifespan and reduce tissue injury in various animal models. Early clinical trials confirm that senotherapeutic approaches could be beneficial in human disease. However, larger clinical trials are needed to translate these approaches to patient care.



中文翻译:


细胞衰老:好的、坏的和未知的



细胞衰老是一个普遍存在的过程,在组织重塑中发挥作用,包括伤口修复和胚胎发生。然而,长期衰老可能会导致适应不良,导致癌症发展和与年龄相关的疾病。细胞衰老涉及细胞周期停滞和具有自分泌、旁分泌和内分泌活性的炎性细胞因子的释放。衰老细胞还表现出形态学改变,包括细胞体变平、细胞质中的空泡化和颗粒度以及异常细胞器。一些细胞衰老的生物标志物已被鉴定,包括 SA-βgal、p16 和 p21;然而,很少有标记物具有高敏感性和特异性。除了加速衰老之外,免疫细胞和实质细胞的衰老还导致多种疾病和代谢紊乱的发生。在肾脏中,衰老可能在发育和损伤恢复过程中发挥有益作用,但也可能导致急性肾损伤和慢性肾脏疾病的进展。针对衰老的治疗,包括抗衰老和抗衰老药物、干细胞疗法和其他干预措施,已被证明可以在各种动物模型中延长寿命并减少组织损伤。早期临床试验证实,治疗方法可能对人类疾病有益。然而,需要更大规模的临床试验来将这些方法转化为患者护理。

更新日期:2022-08-03
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