Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required.

Heavy metals are often found in soil and can contaminate drinking water, posing a serious threat to human health. Molecular pathways and curation therapies for mitigating heavy metal toxicity have been studied for a long time. Recent studies on oxidative stress and aging have shown that the molecular foundation of cellular damage caused by heavy metals, namely, apoptosis, endoplasmic reticulum stress, and mitochondrial stress, share the same pathways as those involved in cellular senescence and aging. In recent aging studies, many types of heavy metal exposures have been used in both cellular and animal aging models. Chelation therapy is a traditional treatment for heavy metal toxicity. However, recently, various antioxidants have been found to be effective in treating heavy metal-induced damage, shifting the research focus to investigating the interplay between antioxidants and heavy metals. In this review, we introduce the molecular basis of heavy metal-induced cellular damage and its relationship with aging, summarize its clinical implications, and discuss antioxidants and other agents with protective effects against heavy metal damage.

Vestibular dysfunction causes postural instability, which is prevalent in the elderly. We previously showed that an imperceptible level of noisy galvanic vestibular stimulation (nGVS) can improve postural stability in patients with bilateral vestibulopathy during the stimulus, presumably by enhancing vestibular information processing. In this study, we investigated the after-effects of an imperceptible long-duration nGVS on body balance in elderly adults. Thirty elderly participants underwent two nGVS sessions in a randomised order. In Session 1, participants received nGVS for 30 min twice with a 4-h interval. In Session 2, participants received nGVS for 3 h. Two-legged stance tasks were performed with eyes closed while participants stood on a foam rubber surface, with and without nGVS, and parameters related to postural stability were measured using posturography. In both sessions, the postural stability was markedly improved for more than 2 h after the cessation of the stimulus and tended to decrease thereafter. The second stimulation in Session 1 caused a moderate additional improvement in body balance and promoted the sustainability of the improvement. These results suggest that nGVS can lead to a postural stability improvement in elderly adults that lasts for several hours after the cessation of the stimulus, probably via vestibular neuroplasticity.

We aimed at determining the mitochondrial function in premature senescence model of auditory cells. Short exposure to H₂O₂ (1 h, 0.1 mM) induced premature cellular senescence in House Ear Institute-Organ of Corti 1 auditory cells. The transmission electron microscopy analysis revealed that damaged mitochondria and autophagosomes containing dense organelles appeared in the auditory cells after short exposure to H₂O₂. The branch and junction parameters of the skeletonized image of the mitochondria were found to decrease significantly in H₂O₂-treated cells. A branched reticulum of tubules was poorly formed, featuring coexistence of numerous tiny clusters along with few relatively large entities in the H₂O₂-treated cells. In terms of bioenergetics, H₂O₂-treatment led to the dose-dependent decrease in mitochondrial membrane potential in the auditory cells. The fragmented mitochondria (fusion < fission) were in a low potential. In addition, the potential of hyperfused mitochondria (fusion > fission) was slightly lower than the control cells. The short-time exposure of live auditory cells to H₂O₂ damaged the mitochondrial respiratory capacity without any effect on the baseline ATP production rates. The vulnerability of the mitochondrial membrane potential to the uncoupling reagent was increased after H₂O₂ treatment. Our findings indicated that the mitochondrial dysfunction due to the decline in the O₂ consumption rate should be the first event of premature senescence process in the auditory cells, resulting in the imbalance of mitochondrial fusion/fission and the collapse of the mitochondrial network.

Objective To assess the frequency-domain characteristics of postural instability caused by peripheral vestibular dysfunction by performing a power spectral analysis of the center of pressure (COP) sway during foam posturography. Methods Data were obtained from 78 patients and 163 controls. Two-legged stance tasks were performed in 4 conditions: eyes open with and without foam rubber, and eyes closed with and without foam rubber. We estimated the power spectrum of the acceleration signal using the maximum entropy method. The areas under the curve (AUCs) of power spectral density of the COP were calculated across low-frequency (0.02 to 0.1 Hz, LF-AUC), middle-frequency (0.1 to 1Hz, MF-AUC), and high-frequency (1 to 10 Hz, HF-AUC) ranges. We performed binomial logistic regression analyses to see whether the AUCs of selected bandwidths of COP have a stronger association with the presence of peripheral vestibular dysfunction in comparison with the velocity and area in the eyes closed/foam rubber condition. Results In both the controls and patients, the MF-AUC was significantly larger than the LF-AUC or HF-AUC in the eyes closed/foam rubber condition. In this condition, the presence of peripheral vestibular dysfunction had a significantly positive relationship with MF-AUC and HF-AUC (p < 0.05) and the MF-AUC of the anterior-posterior axis showed a stronger association with the presence of peripheral vestibular dysfunction than area. Conclusion An increase in activity at middle frequency movements could be characteristic of peripheral vestibular dysfunction when standing on foam rubber with the eyes closed.

The aim of this study was to investigate the effects of pyrroloquinoline quinone (PQQ), an oxidoreductase cofactor, on the H₂O₂-induced premature senescence model in HEI-OC1 auditory cells and to elucidate its mechanism of action in vitro. Cells were treated with PQQ for 1 day before H₂O₂(100 μM) exposure. Mitochondrial respiratory capacity was damaged in this premature senescence model but was restored in cells pretreated with PQQ (0.1 nM or 1.0 nM). A decrease in mitochondrial potential, the promotion of mitochondrial fusion and the accelerated movement of mitochondria were all observed in PQQ-pretreated cells. The protein expression of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) were significantly decreased under H₂O₂exposure while they were increased with PQQ pretreatment, and PGC-1α acetylation was significantly decreased. In conclusion, PQQ has a protective effect on the premature senescence model of HEI-OC1 auditory cells and is associated with the SIRT1/PGC-1α signaling pathway, mitochondrial structure, and mitochondrial respiratory capacity.