Senolytic Targeting of Anti-Apoptotic Bcl Family Increases Cell Death in UV-Irradiated Senescent Melanocytes: Search for Senolytics

Abstract

Senescent melanocytes have been suggested to play a role in the development of ageing-associated pigmentary changes and skin ageing. Here, we assessed the senolytic capacity of recognised senolytic chemicals and natural compounds in UV-irradiated senescent melanocytes. Among the tested agents, only ABT-737 and ABT-263 showed a significant reduction in the number of SA-β-Gal-positive senescent melanocytes and in the expressions of p16^INK4A and p21^Waf1. The senolytic effects of the ABT drugs were associated with increased expression of cleaved caspase-3, which was hindered with a caspase inhibitor, Z-VAD. These findings indicate that ABT-737 and ABT-263 eliminate senescent melanocytes through caspase-mediated apoptosis, suggesting their future potential to address ageing skin.