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Senolytic Targeting of Anti-Apoptotic Bcl Family Increases Cell Death in UV-Irradiated Senescent Melanocytes: Search
Jin Cheol Kim1,2, Na Yeon Kim1,3, Yeongeun Kim1,2
1Department of Dermatology, Ajou University School of Medicine; Suwon, Suwon, Korea.
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 p16INK4A and p21Waf1. 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.
Insights
Senescent melanocytes contribute to skin aging. ABT-737 and ABT-263 effectively cleared these cells via apoptosis, indicating potential for anti-aging skin treatments.
Area of Science:
- Dermatology
- Cell Biology
- Gerontology
Background:
- Senescent melanocytes are implicated in age-related skin changes and hyperpigmentation.
- Cellular senescence contributes to the aging phenotype of the skin.
Purpose of the Study:
- To evaluate the senolytic potential of various compounds on UV-induced senescent melanocytes.
- To investigate the mechanisms underlying the senolytic activity of effective compounds.
Main Methods:
- UV irradiation was used to induce senescence in melanocytes.
- Senescent cells were treated with known senolytic chemicals and natural compounds.
- Key markers of senescence (SA-β-Gal, p16INK4A, p21Waf1) and apoptosis (cleaved caspase-3) were assessed.
Main Results:
- ABT-737 and ABT-263 significantly reduced senescent melanocyte populations.
- These drugs decreased the expression of senescence markers p16INK4A and p21Waf1.
- Senolytic effects were linked to increased cleaved caspase-3, blocked by the caspase inhibitor Z-VAD.
Conclusions:
- ABT-737 and ABT-263 demonstrate senolytic capacity by inducing apoptosis in senescent melanocytes.
- The findings suggest these compounds may be beneficial for targeting age-related skin conditions.
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