Senescent Cells in Early Vascular Ageing and Bone Disease of Chronic Kidney Disease-A Novel Target for Treatment

Abstract

Together with bone-mineral disorders, premature vascular ageing is a common feature of the uremic phenotype. A detailed understanding of mechanisms involved remains unclear and warrants further research. Available treatment options for end stage renal disease are principally dialysis and organ transplantation, as other treatment alternatives have proven insufficient. Chronic kidney disease (CKD) has been proposed as a model of early vascular and bone ageing, with accumulating evidence supporting the contribution of cellular senescence and the senescence-associated secretory phenotype (SASP) to cardiovascular pathology in CKD. Correspondingly, novel therapies based around the use of senolytic compounds and nuclear factor-erythroid-2-related factor 2 (Nrf2) agonists, have been suggested as attractive novel treatment options. In this review, we detail the contribution of the uremic environment to these processes underpinning ageing and how these relate to vascular health.

Keywords: Nrf2; ageing; chronic kidney disease; senescence; uremic toxins.

Figure 1

A schematic view of the pathways, molecular mechanisms and cell types inducing cellular senescence, thus leading to chronic age-related diseases. C/EBP-β, CCAAT/enhancer binding protein-β; IL-1β, interleukin 1β; IL-6, interleukin 6; NF-κB, nuclear factor κB; ROS, reactive oxygen species; TGF-β, transforming growth factor β; nuclear factor-erythroid-2-related factor 2, Nrf2. Adapted from Tchkonia et al. 2013 [19].