Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, Gangwon-do 26426, Korea.
Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, wonju 26493, Korea.
Int J Mol Sci. 2020 Sep 25;21(19):7068. doi: 10.3390/ijms21197068.
Age-related hearing loss (ARHL) is the most common sensory disorder among the elderly, associated with aging and auditory hair cell death due to oxidative-stress-induced mitochondrial dysfunction. Although transgenic mice and long-term aging induction cultures have been used to study ARHL, there are currently no ARHL animal models that can be stimulated by intermittent environmental changes. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined on the basis of expression of hearing-loss-induced phenotypes and aging-related factors. The incidence of hearing loss was significantly higher in dual- and triple-exposure conditions than in intermittent hypoxic conditions, high-fat diet (HFD), or d-galactose injection alone. Continuous oxidative stress and HFD accelerated cellular aging. An increase in usually expressed during mitochondrial dysfunction, was observed. Expression of , , , , and , which are ARHL-related factors, were modified by oxidative stress in the cells of the hearing organ. We found that intermittent hypoxia, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects the effects of intermittent environmental changes, will benefit future research on ARHL.
年龄相关性听力损失(ARHL)是老年人最常见的感觉障碍,与衰老和听觉毛细胞死亡有关,这是由于氧化应激引起的线粒体功能障碍。虽然已经使用转基因小鼠和长期衰老诱导培养物来研究 ARHL,但目前尚无可通过间歇性环境变化刺激的 ARHL 动物模型。在这项研究中,通过诱导持续的氧化应激来建立 ARHL 动物模型,以促进细胞的短期衰老,这是基于听力损失诱导表型和与衰老相关的因素的表达来确定的。与间歇性低氧、高脂肪饮食(HFD)或单独注射 D-半乳糖相比,双重和三重暴露条件下听力损失的发生率明显更高。持续的氧化应激和 HFD 加速了细胞衰老。通常在线粒体功能障碍期间表达增加。氧化应激会改变听力器官细胞中与 ARHL 相关的因子 、 、 、 和 的表达。我们发现间歇性低氧、HFD 和半乳糖注射会加速短期细胞衰老。因此,我们预计这种反映间歇性环境变化影响的听力损失动物模型的发展将有益于未来对 ARHL 的研究。