Peer-review started: July 1, 2014
First decision: October 14, 2014
Revised: October 28, 2014
Accepted: November 17, 2014
Article in press: November 19, 2014
Published online: February 6, 2015
Processing time: 221 Days and 12.5 Hours
Many observers have noted that the morphological changes that occur in chronic kidney disease (CKD) patients resemble those seen in the geriatric population, with strikingly similar morbidity and mortality profiles and rates of frailty in the two groups, and shared characteristics at a pathophysiological level especially in respect to the changes seen in their vascular and immune systems. However, whilst much has been documented about the shared physical characteristics of aging and uremia, the molecular and cellular similarities between the two have received less attention. In order to bridge this perceived gap we have reviewed published research concerning the common molecular processes seen in aging subjects and CKD patients, with specific attention to altered proteostasis, mitochondrial dysfunction, post-translational protein modification, and senescence and telomere attrition. We have also sought to illustrate how the cell death and survival pathways apoptosis, necroptosis and autophagy are closely interrelated, and how an understanding of these overlapping pathways is helpful in order to appreciate the shared molecular basis behind the pathophysiology of aging and uremia. This analysis revealed many common molecular characteristics and showed similar patterns of cellular dysfunction. We conclude that the accelerated aging seen in patients with CKD is underpinned at the molecular level, and that a greater understanding of these molecular processes might eventually lead to new much needed therapeutic strategies of benefit to patients with renal disease.
Core tip: This review presents evidence that suggests that the morphological similarities between uremia and physiological aging are underpinned by similarities at a cellular and molecular level. Several of the classical cellular features of aging such as mitochondrial dysfunction and altered proteostasis have been observed in the cells and tissues of uremic humans and animals, and in in vitro models of uremia. There are also many shared features between aging and uremia in terms of cell death and survival pathways. These commonalities may present new targets for the future management of patients with chronic kidney disease.