Targeting Senescent Cells as Therapy for CKD

Abstract

Senescent cells accumulate in the kidney with ageing, after acute and chronic injuries, and are present in increased numbers in deteriorating kidney transplants. Senescent cells have undergone permanent cell-cycle arrest and release many proinflammatory cytokines/chemokines and pro-fibrotic factors: the senescence-associated secretory phenotype (SASP). Recent work from several groups including our own has shown that senescent cells play a causative role in progression of kidney disease. Experimental evidence also indicates that targeting senescent cells has potential to alter the renal regenerative response, reducing progressive fibrosis and improving functional recovery after injury. Research and clinical interest is focused on understanding how accumulating chronic senescent cells link acute injury to progressive fibrosis, dysfunction and mortality in human CKD.