Miwa Toru
Department of Otolaryngology and Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
Department of Otolaryngology and Head and Neck Surgery, Graduate of School of Medicine, Kyoto University, Kyoto, Japan.
Front Cell Neurosci. 2021 Apr 6;15:634868. doi: 10.3389/fncel.2021.634868. eCollection 2021.
Age-related hearing loss (ARHL) is the most common form of hearing loss and the predominant neurodegenerative disease associated with aging. is associated with the most complex physiological processes, including metabolism, cancer onset, and aging. SIRT1 protein levels are enhanced by the conversion of nicotinamide to N-methylnicotinamide (MNAM), independent of its mRNA levels. Moreover, MNAM has implications in increased longevity achieved through its mitohormetic effects. Nicotinamide N-methyltransferase (Nnmt) is an enzyme involved in MNAM metabolism, and its level increases under caloric restriction (CR) conditions. The CR condition has implications in delaying ARHL onset. In this study, we aimed to determine the relationship between diet, hearing function, SIRT1 and SIRT3 expression levels in the inner ear, and cochlear morphology. Mice fed with a high-fat diet (HFD), HFD + 1% MNAM, and low-fat diet (LFD) were monitored for age-related auditory-evoked brainstem responses, and changes in cochlear histology, metabolism, and protein and mRNA expressions were analyzed. Our results revealed that the HFD- and aging-mediated downregulated expression of SIRT1 and SIRT3 promoted hearing loss that was obfuscated by MNAM supplementation-induced upregulated expression of cochlear SIRT1 and SIRT3. Thus, our results suggest that MNAM can be used as a therapeutic agent for preventing ARHL.
年龄相关性听力损失（ARHL）是最常见的听力损失形式，也是与衰老相关的主要神经退行性疾病。它与最复杂的生理过程相关，包括新陈代谢、癌症发生和衰老。烟酰胺转化为N-甲基烟酰胺（MNAM）可提高SIRT1蛋白水平，而与其mRNA水平无关。此外，MNAM通过其线粒体应激效应延长寿命。烟酰胺N-甲基转移酶（Nnmt）是一种参与MNAM代谢的酶，其水平在热量限制（CR）条件下会升高。CR条件对延缓ARHL发病有影响。在本研究中，我们旨在确定饮食、听力功能、内耳中SIRT1和SIRT3表达水平以及耳蜗形态之间的关系。对喂食高脂饮食（HFD）、HFD + 1% MNAM和低脂饮食（LFD）的小鼠进行年龄相关性听觉诱发电位脑干反应监测，并分析耳蜗组织学、代谢以及蛋白质和mRNA表达的变化。我们的结果显示，HFD和衰老介导的SIRT1和SIRT3表达下调促进了听力损失，而MNAM补充诱导的耳蜗SIRT1和SIRT3表达上调则掩盖了这种损失。因此，我们的结果表明MNAM可用作预防ARHL的治疗剂。
