Epac1 Alleviates Senescence in Auditory Hair Cells via the Ferroptosis

ABSTRACT Objectives The aim of this study was to investigate the changes in Epac1 and ferroptosis‐related proteins in aged mice and the House Ear Institute‐Organ of Corti 1 (HEI‐OC1) cells, with the goal of elucidating their potential role in age‐related hearing loss. Methods The expression of Epac1 in the cochlea of C57BL/6J mice was examined by using immunofluorescence staining and Western blot analysis. To further verify the role of Epac1 in age‐related hearing loss, small interfering RNA (siRNA) was transfected into HEI‐OC1 cells, resulting in the downregulation of Epac1. Results The results revealed a decrease in Epac1 expression in the cochlea of aged mice. After downregulating the level of Epac1 in vitro, a greater level of ferroptosis was observed, and the aging process was accelerated. Conclusions Epac1 plays a crucial role in the aging process of auditory hair cells via ferroptosis.