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.