Cellular senescence in renal ageing and disease

Abstract

The senescence programme is implicated in diverse biological processes, including embryogenesis, tissue regeneration and repair, tumorigenesis, and ageing. Although in vivo studies of senescence are in their infancy, evidence suggesting that senescent cells are a heterogeneous cell type is accumulating: senescence can be induced by different stressors, and senescent cells have varying degrees of genomic and epigenomic instability and different cell origins, contributing to their diversity. Two main classes of senescent cells have been identified: acute and chronic senescent cells. Acute senescent cells are generated during coordinated, beneficial biological processes characterized by a defined senescence trigger, transient senescent-cell signalling functions, and eventual senescent-cell clearance. In contrast, chronic senescent cells arise more slowly from cumulative, diverse stresses and are inefficiently eliminated, leading to their accumulation and deleterious effects through a secretory phenotype. Senescent cells have been identified in many tissues and organs, including the kidney. Here, we discuss the emerging roles of senescent cells in renal development, homeostasis, and pathology. We also address how senotherapy, or targeting of senescent cells, might be used to improve renal function with normal ageing, disease, or therapy-induced damage.