Sestrin2 Mediates Hair Cell Oxidative Stress in Delaying Age-Related Hearing Loss
WANG Liwen
JIANG Linlan
GAO Shuyi
JIAO Yuenong
Abstract：Objective Sestrin2 is a key antioxidant protein.This study aims to investigate the effects of the Sestrin2 gene on oxidative stress in hair cells and on age-related hearing loss(ARHL)in mice.Methods H2O2 was used to induce oxidative stress senescence in HEI-OC1 cells and in a C57BL/6 mice aging model,and the adeno-associated virus technology was employed to establish Sestrin2 overexpression and knockout models...The effects of Sestrin2 on HEI-OC1 cells under oxidative stress were analyzed through measurement of reactive oxygen species(ROS)and β-galactosidase staining.Additionally,Sestrin2 protein levels in the mouse cochlea were quantified via Western blot.Mitochondrial membrane potentials(MMP)and auditory brainstem responses(ABRs)testing were used to evaluate the effects of Sestrin2 on aging mice.Results Compared with the controls,the Sestrin2 overexpression group exhibited significantly reduced ROS levels(P<0.001)and a decrease in HEI-OC1 cell nuclear area(P<0.0001).Furthermore,mice with Sestrin2 overexpression showed significantly better ABR thresholds at 4 and 8 kHz(P<0.001),accompanied by significantly increased MMP(P<0.0001).Conclusion Sestrin2 reduces oxidative stress in hair cells,counteracts hair cell aging,and delays ARHL.
Keywords：Sestrin2HEI-OC1age-related hearing lossreactive oxygen species
Publication Date：2025-09-20
Online Publishing Date：2025-09-15(First online date of this platform, not the publication date of the document)
Pages：5( 785-789 )