Early vascular ageing and cellular senescence in chronic kidney disease

Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by progressive vascular dis- ease, systemic inflammation, muscle wasting and frailty. The predominant early vascular ageing (EVA) process mediated by medial vascular calcification (VC) results in a marked discrepancy between chronological and bio- logical vascular age in CKD. Though the exact underlying mechanisms of VC and EVA are not fully elucidated, ac- cumulating evidence indicates that cellular senescence - and subsequent chronic inflammation through the senescence-associated secretary phenotype (SASP) - plays a fundamental role in its initiation and progression. In this review, we discuss the pathophysiological links between senescence and the EVA process in CKD, with focus on cellular senescence and media VC, and potential anti-ageing therapeutic strategies of senolytic drugs targeting cellular senescence and EVA in CKD.Swedish Research Council (grant no 2009-1068)European Union‘s Horizon 2020 research and innovation Program, Marie Skłodowska-Curie (grant agreement No 722609)International Network for Training on Risks of Vascular Intimal Calcification and roads to Regression of Cardiovascular Disease (INTRICARE)Baxter HealthcarePublishe