Cellular senescence as a therapeutic target to improve renal transplantation outcome
Kidney transplants from aged donors are more vulnerable to ischemic injury, suffer more from delayed graft function and have a lower graft survival compared to kidneys from younger donors. On a cellular level, aging results in an increase in cells that are in a permanent cell cycle arrest, termed senescence, which secrete a range of pro-inflammatory cytokines and growth factors. Consequently, these senescent cells negatively influence the local milieu by causing inflammaging, and by reducing the regenerative capacity of the kidney. Moreover, the oxidative damage that is inflicted by ischemia-reperfusion injury during transplantation can induce senescence and accelerate aging.In this review, we describe recent developments in the understanding of the biology of aging that have led to the development of a new class of therapeutic agents aimed at eliminating senescent cells. These compounds have already shown to be able to restore tissue homeostasis in old mice, improve kidney function and general health- and lifespan. Use of these anti-senescence compounds holds great promise to improve the quality of marginal donor kidneys as well as to remove senescent cells induced by ischemia-reperfusion injury. Altogether, senescent cell removal may increase the donor pool, relieving the growing organ shortage and improve long-term transplantation outcome.
|A1155463, A1331852, Alvespimycin (17-DMAG), Anti-senescence compounds, Dasatinib, FOXO4-DRI, FOXO4-DRI, Ischemia-reperfusion injury, Navitoclax, Navitoclax (ABT-263), Quercetin, Renal transplantation, Senescence|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
van Willigenburg, H. (Hester), de Keizer, P.L.J, & de Bruin, R.W.F. (2018). Cellular senescence as a therapeutic target to improve renal transplantation outcome. Pharmacological Research. doi:10.1016/j.phrs.2018.02.015