Targeting kidney cell senescence: a new paradigm for the treatment of chronic kidney disease?

Abstract

Cellular senescence is a condition where cells undergo a permanent cell cycle arrest, accompanied by a unique set of functional and morphological changes. While initial studies of senescence have largely focused on its role as a barrier to extended cell division and tumorigenesis, in recent years cell senescence has emerged as an important driver of aging and age-related disease in different tissues, including the kidney. Accelerated cell senescence may decrease kidney repair capacity because of cell cycle arrest; in addition cell senescence promotes glomerulosclerosis and tubulointerstitial fibrosis via the production and release of proinflammatory and matrix-degrading molecules. Although almost all glomerular and tubular cells may undergo senescent changes, the glomerular podocytes and proximal tubule cells are the most commonly affected cells. In these days, treating cell senescence is moving his steps from the preclinical to the clinical stage. While cell senescence appears to be well accepted as a new mechanism for kidney damage and chronic kidney disease [CKD] progression, there still are many unanswered questions regarding how to dectect it in kidney biopsies, which is prognostic meaning of individual kidney senescnce markers, which the role of different cells involved, as well as the efficacy of the emerging senescence-targeted therapies on the progression and complications of CKD.