Podocyte Senescence and Aging

Abstract

As the population in many industrial countries is aging, the risk, incidence, and prevalence of chronic kidney diseases (CKD) increases. In the kidney, advancing age results in a progressive decrease in nephron number and an increase in glomerulosclerosis. In this review, we focus on the impact of aging on glomerular podocytes, the post-mitotic epithelial cells critical for the normal integrity and function of the glomerular filtration barrier. The podocytes undergo senescence and transition to a senescent-associated secretory phenotype typified by the production and secretion of inflammatory cytokines that can influence neighboring glomerular cells by paracrine signaling. In addition to senescence, the aging podocyte phenotype is characterized by ultrastructural and functional changes, hypertrophy, cellular, oxidative and endoplasmic reticulum stress, reduced autophagy and increased expression of aging genes. This results in a reduced podocyte health-span and a shortened lifespan. Importantly, these changes in the pathways/processes characteristic of healthy podocytes aging are also often similar to pathways in the disease-induced injured podocyte. Finally, the better understanding of podocyte aging and senescence opens therapeutic options to slow the rate of podocyte aging and promote kidney health.