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 ultraviolet (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 11 (GDF11) can attenuate UVB-induced damage. Our findings indicate that cumulative UVB irradiation induces photodaging in sebocytes, characterized by impaired cellular function and upregulation 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 (ROS), decreased expression of the ferroptosis-related protein GPX4, and elevated levels of ACSL4 and NCOA4. Further experiments confirmed that GDF11 overexpression increased proportion of apoptotic cells and downregulated GPX4 and ACSL4 expression, whereas GDF11 knockdown produced the opposite effects. These results suggest that GDF11 mitigates sebocyte photoaing via ferroptosis pathway and highlight its potential as a therapeutic target.