Growth Differentiation Factor 11 Attenuates Photoaging through Ferroptosis Pathway in SZ95 Sebocytes

Sebaceous glands synthesize and secrete sebum, forming a protective barrier on the skin. However, prolonged exposure to UV radiation leads to glandular atrophy and reduced sebum production. This study investigated the impact of UVB irradiation on sebocyte function and demonstrated that growth differentiation factor (GDF)-11 can attenuate UVB-induced damage. The findings indicate that cumulative UVB irradiation induces photoaging in sebocytes, characterized by impaired cellular function and up-regulation of cellular senescence markers, along with reduced GDF11 expression. Notably, GDF11 overexpression alleviated these adverse effects. Apoptosis assays revealed that photoaged sebaceous gland cells exhibited resistance to apoptosis. Transmission electron microscopy further identified features indicative of ferroptosis. UVB exposure led to increased intracellular reactive oxygen species, decreased expression of the ferroptosis-related protein glutathione peroxidase (GPX)-4, and elevated levels of long-chain fatty acid-CoA ligase (ACSL)-4 and nuclear receptor coactivator (NCOA)-4. Further experiments confirmed that GDF11 overexpression increased the percentage of apoptotic cells and down-regulated GPX4 and ACSL4 expression, whereas GDF11 knockdown produced the opposite effects. These results suggest that GDF11 mitigates sebocyte photoaging via the ferroptosis pathway and highlight its potential as a therapeutic target.