Fetoni Anna Rita, Pisani Anna, Rolesi Rolando, Paciello Fabiola, Viziano Andrea, Moleti Arturo, Sisto Renata, Troiani Diana, Paludetti Gaetano, Grassi Claudio
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Department of Otolaryngology Head and Neck Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
Front Aging Neurosci. 2022 Feb 7;14:803973. doi: 10.3389/fnagi.2022.803973. eCollection 2022.
Several studies identified hearing loss as a risk factor for aging-related processes, including neurodegenerative diseases, as dementia and age-related hearing loss (ARHL). Although the association between hearing impairment in midlife and ARHL has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood. In this study, we used an established animal model of ARHL (C57BL/6 mice) to evaluate if early noise-induced hearing loss (NIHL) could affect the onset or progression of age-related cochlear dysfunction. We found that hearing loss can exacerbate ARHL, damaging sensory-neural cochlear epithelium and causing synaptopathy. Moreover, we studied common pathological markers shared between hearing loss and ARHL, demonstrating that noise exposure can worsen/accelerate redox status imbalance [increase of reactive oxygen species (ROS) production, lipid peroxidation, and dysregulation of endogenous antioxidant response] and vascular dysfunction [increased expression of hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor C (VEGFC)] in the cochlea. Unveiling the molecular mechanisms underlying the link between hearing loss and aging processes could be valuable to identify effective therapeutic strategies to limit the effect of environmental risk factors on age-related diseases.
多项研究将听力损失确定为与衰老相关过程的风险因素,包括神经退行性疾病,如痴呆症和年龄相关性听力损失(ARHL)。尽管中年听力障碍与ARHL之间的关联已被流行病学和实验研究广泛记录,但这种关联背后的分子机制尚未完全了解。在本研究中,我们使用已建立的ARHL动物模型(C57BL/6小鼠)来评估早期噪声性听力损失(NIHL)是否会影响年龄相关性耳蜗功能障碍的发生或进展。我们发现听力损失会加剧ARHL,损害感觉神经性耳蜗上皮并导致突触病变。此外,我们研究了听力损失和ARHL之间共有的常见病理标志物,表明噪声暴露会使耳蜗中的氧化还原状态失衡(活性氧(ROS)产生增加、脂质过氧化和内源性抗氧化反应失调)和血管功能障碍(缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子C(VEGFC)表达增加)恶化/加速。揭示听力损失与衰老过程之间联系的分子机制对于确定有效的治疗策略以限制环境风险因素对年龄相关性疾病的影响可能具有重要价值。