Stress-induced senescence as a forme fruste of chronic kidney disease—A case for failed regeneration

Abstract This chapter summarizes multiple points of convergence between chronic kidney disease and kidney senescence to highlight the proposition that both entities are deeply intertwined. Next, I describe geronic proteins using as an example the interactions between endostatin and tissue transglutaminase. I propose that the stress-induced premature senescence of kidney-resident cells constitutes a platform for progression of chronic kidney disease. The description of fate of senescent cells from enforced rejuvenation to a point of no-return or apoptosis follows. Local and systemic effects of senescent cells, including the release of senescence-associated secretory phenotype products, are delineated. The chapter concludes with the recounting of therapeutic strategies to limit the senescent cell burden and, by doing so, arresting the progression of chronic kidney disease.