LCN2 promotes HEI-OC1 cells senescence via activating NF-κB signal pathway in presbycusis.

Abstract

Presbycusis, or age-related hearing loss (ARHL), is a prevalent sensory disorder in the elderly, driven by genetic factors, oxidative stress, inflammation responses, and cellular senescence. Despite its significance, the molecular mechanisms underlying ARHL remain poorly defined. In this study, we employed bioinformatic analysis of public gene expression datasets to identify differentially expressed genes in ARHL. Protein-protein interaction network analysis further nominated LCN2 as a hub gene. Experimental validation in aging C57BL/6J mice and HEI-OC1 auditory cells revealed that elevated LCN2 expression promotes cellular senescence, while its knockdown delays this phenotype. Mechanistically, LCN2 drives senescence by activating the NF-κB signaling pathway, and its inhibition alleviates senescence induced by tert-butyl hydroperoxide (TBHP). Our findings establish LCN2 as a key pro-senescence factor in ARHL and demonstrate that it regulates auditory cell senescence through the NF-κB pathway, providing new mechanistic insights and revealing potential therapeutic targets for ARHL intervention.