Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Biochemistry, Cardiovascular Research School Maastricht, Maastricht University, Maastricht, The Netherlands.
Nephrol Dial Transplant. 2020 Mar 1;35(Suppl 2):ii31-ii37. doi: 10.1093/ndt/gfaa006.
Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by cardiovascular disease, persistent uraemic inflammation, osteoporosis muscle wasting and frailty. The accelerated early vascular ageing (EVA) process mediated by medial vascular calcification (VC) is a hallmark of senescence as well as a strong predictor of cardiovascular morbidity and mortality in the CKD population. Current clinical therapeutic strategies and novel treatments for VC have not yet been proven to prevent or reverse VC progression in patients with CKD. Knowledge of the fundamental mechanism underlying EVA is urgently needed to identify and develop novel and efficient therapeutic targets for VC and EVA. An accumulating body of evidence indicates that deoxyribonucleic acid (DNA) damage-induced cellular senescence and 'inflammaging' may largely contribute to such pathological conditions characterized by accelerated EVA. Growing evidence shows that nuclear factor erythroid 2-related factor 2 (NRF2) signalling and vitamin K play a crucial role in counteracting oxidative stress, DNA damage, senescence and inflammaging, whereby NRF2 activation and vitamin K supplementation may provide a novel treatment target for EVA. In this review we discuss the link between senescence and EVA in the context of CKD, with a focus on the role of NRF2 and vitamin K in DNA damage signalling, senescence and inflammaging.
慢性肾脏病（CKD）是一种过早衰老的临床模型，其特征是心血管疾病、持续性尿毒症炎症、骨质疏松症、肌肉减少和虚弱。由中膜血管钙化（VC）介导的加速早期血管衰老（EVA）过程是衰老的标志，也是 CKD 人群心血管发病率和死亡率的强有力预测指标。目前针对 VC 的临床治疗策略和新疗法尚未被证明能预防或逆转 CKD 患者的 VC 进展。急需了解 EVA 背后的基本机制，以确定和开发针对 VC 和 EVA 的新型有效治疗靶点。越来越多的证据表明，脱氧核糖核酸（DNA）损伤诱导的细胞衰老和“炎老化”可能在很大程度上导致 EVA 加速等病理状况。越来越多的证据表明，核因子红细胞 2 相关因子 2（NRF2）信号和维生素 K 在对抗氧化应激、DNA 损伤、衰老和炎老化方面发挥着关键作用，NRF2 激活和维生素 K 补充可能为 EVA 提供新的治疗靶点。在这篇综述中，我们讨论了衰老与 CKD 中 EVA 的联系，重点介绍了 NRF2 和维生素 K 在 DNA 损伤信号、衰老和炎老化中的作用。
