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.
Highlights
Ageing is characterised by a decline in functional physiological capability over the life course.The rate of ageing can be manipulated experimentally, significant, therapeutic intervention to mitigate physiological decline remains largely limited to pre-clinical models [1]
Hydroxyapatite crystal deposition can present in the tunica media, intima or cardiac valves, a complication of chronic kidney disease (CKD)–MBD [48] that is strongly associated with high cardiovascular mortality in this patient population [49]
CKD is characterised by a persistent low-grade inflammation, with factors such as dialysis membranes, oxidative stress, microbial factors, uremic toxins, and cellular senescence contributing to the increased inflammatory microenvironment [51]
Summary
Ageing is characterised by a decline in functional physiological capability over the life course. Recent experimental evidence in pre-clinical models has shown that senolytic drugs (which promote effective removal of senescent cells) prolongs the health span and lifespan in mice by up to 36% [16], supporting the initiation of preclinical studies with senolytic drugs in the uremic milieu. Whether this translates into humans remains to be determined [17]. Adapted from Tchkonia et al 2013 [19]
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