Wakino Shu, Itoh Hiroshi
Nihon Rinsho. 2016 Sep;74(9):1531-1540.
Kidney is an energy-consuming organ and its function deteriorates according as aging. Various mechanisms for cellular senescence and organ aging have an impact on the initiation and progression of CKD, which includes telomere attrition, genomic instability, stem cell exhaustion, mitochondrial dysfunction, impaired nutrient signaling, inactivation of Sirtuin or Klotho-mediated pathway and renin-angiotensin system activation. Interventions in these pathways have provided therapeutic strategy against CKD. On the other hand, renal dys- function, in turn, affects human aging process. Because of this close relationship between human aging process and CKD, aging phenotype, such as frailty can be used as a clinical marker of the prognosis of CKD as well as of other age-related diseases including cardio- vascular disease and type II diabetes. Amelioration of this aging phenotype can provide a novel therapeutic strategy against CKD for the purpose of providing CKD patients with suc- cessful aging.
肾脏是一个耗能器官,其功能会随着衰老而恶化。细胞衰老和器官老化的各种机制会影响慢性肾脏病(CKD)的发生和发展,其中包括端粒磨损、基因组不稳定、干细胞耗竭、线粒体功能障碍、营养信号受损、沉默调节蛋白或α-klotho介导途径失活以及肾素-血管紧张素系统激活。对这些途径的干预为CKD提供了治疗策略。另一方面,肾功能障碍反过来又会影响人类衰老过程。由于人类衰老过程与CKD之间存在这种密切关系,诸如虚弱等衰老表型可作为CKD以及包括心血管疾病和II型糖尿病在内的其他与年龄相关疾病预后的临床标志物。改善这种衰老表型可为CKD提供一种新的治疗策略,以使CKD患者能够成功衰老。