Upregulation of the Ca_v1.3 channel in inner hair cells by interleukin 6-dependent inflammaging contributes to age-related hearing loss.

IF 8 1区医学 Q1 CELL BIOLOGY

Aging Cell Pub Date : 2024-08-15 DOI:10.1111/acel.14305

Mingshun Lu, Fuyu Xian, Xishuo Jin, Guodong Hong, Xiaolong Fu, Shengnan Wang, Xinyu Li, Haichao Yang, Hongchen Li, Haiwei Zhang, Yuxin Yang, Jundan Xiao, Hui Dong, Yaling Liu, Haitao Shen, Ping Lv

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Abstract

Age-related hearing loss (AHL) is the most common sensory disorder amongst the older population. Inflammaging is a ≈chronic low-grade inflammation that worsens with age and is an early sign of AHL; however, the underlying mechanisms remain unclear. We used electrophysiological and genetic approaches to establish the importance of interleukin 6 (IL-6)-dependent inflammation in AHL. Elevated IL-6 in the cochlea enhanced Ca_v1.3 calcium channel function in the inner hair cell (IHC) synapse in mice with AHL. IL-6 upregulated the Ca_v1.3 channel via the Janus kinase-mitogen activated kinase pathway, causing neurotransmitter excitotoxicity and synapse impairment; IL-6 deficiency or the administration of a Ca_v1.3 channel blocker attenuated this age-related damage, and rescued hearing loss. Thus, IL-6-dependent inflammaging upregulated the Ca_v1.3 channel in IHCs, contributing to AHL. Our findings could help the comprehensive understanding of inflammaging's effects on AHL, aiding in early intervention to protect against hearing decline.

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白细胞介素 6 依赖性炎症上调内毛细胞中的 Cav1.3 通道，导致老年性听力损失。

老年性听力损失（AHL）是老年人口中最常见的感官障碍。炎症是一种≈慢性的低度炎症，会随着年龄的增长而恶化，是 AHL 的早期征兆；然而，其潜在机制仍不清楚。我们利用电生理学和遗传学方法确定了白细胞介素 6（IL-6）依赖性炎症在 AHL 中的重要性。患有 AHL 的小鼠耳蜗中升高的 IL-6 增强了内毛细胞（IHC）突触中 Cav1.3 钙通道的功能。IL-6通过Janus激酶-丝裂原活化激酶途径上调Cav1.3通道，导致神经递质兴奋毒性和突触损伤；IL-6缺乏或服用Cav1.3通道阻断剂可减轻这种与年龄相关的损伤，并挽救听力损失。因此，IL-6依赖性炎症上调了IHCs中的Cav1.3通道，导致了AHL。我们的发现有助于全面了解炎症对AHL的影响，有助于早期干预以防止听力下降。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology

自引率

2.60%

发文量

212

期刊介绍： Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.

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