Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss

Abstract

Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, β-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells’ senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.

Downregulation of REST in the cochlea contributes to age-related hearing loss via the p53 apoptosis pathway

“…H 2 O 2 is the most common agent inducing senescence because it naturally induces oxidative stress, which can cause premature senescence in auditory cells, resulting in AHL [ 41 ]. The model of senescence induced by H 2 O 2 in the HEI-OC1 cell lines, can be a useful tool to study the intrinsic mechanisms responsible for AHL in vitro [ 42 ]. In this study, we found that REST knockdown by siRNA increases the expression of p53 and cleaved caspase-3 in HEI-OC1 cells.…”

Role of the Stria Vascularis in the Pathogenesis of Sensorineural Hearing Loss: A Narrative Review

“…For example, all ototoxic drugs must cross the BLB to enter the inner ear tissues to exert their cytotoxic effects and induce hearing loss; therefore, extensive vacuolization in the SV has always been observed in related investigations. Moreover, the inner ear has been considered an immune-privileged site because of the presence of BLB (Rivas-Chacón et al, 2021). Autoimmune inner ear disease usually manifests as immunoglobulin G deposition in the SV.…”

“…Luz and Jiang conducted experiments in SV-k1 cell lines (from SV) and primary marginal cells of the SV, respectively (Jiang et al, 2018;Rivas-Chacón et al, 2021), to explore the oxidative stress mechanism in SV in ARHL. Recently, researchers have identified age-related changes in the morphology and number of macrophages in the human SV, and suggested that further investigations of the role of macrophage-associated inflammation in SV in ARHL are necessary (Noble et al, 2019).…”

Age-Related Hearing Loss: The Link between Inflammaging, Immunosenescence, and Gut Dysbiosis

“…However, multiple stressors can result in ROS overproduction and tissue accumulation [22,134] Accumulation of ROS and other free radicals can impair DNA and break down cellular proteins and lipids, contributing to apoptotic cell death in the cochlea [85]. OS also contributes to the cellular senescence pattern in the ageing cochlea [1]. Rivas-Chacon and colleagues reported that OS and premature senescence significantly impaired cell viability in three auditory cell lines (HEI-OC1, OC-k3, and SV-k1) [1].…”

“…Age-related hearing loss (ARHL), or presbyacusis, is a type of sensorineural hearing loss that primarily affects the elderly [1]. However, the age of onset, rate of decline, and severity of hearing loss vary widely.…”