Upregulation of the Ca<sub>v</sub>1.3 channel in inner hair cells by interleukin 6‐dependent inflammaging contributes to age‐related hearing loss-Reference-Cited by-同舟云学术

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

Published:2024-08-15 Issue: Volume: Page:
ISSN:1474-9718
Container-title:Aging Cell
language:en
Short-container-title:Aging Cell

Author:

Lu Mingshun¹^ORCID,Xian Fuyu¹,Jin Xishuo¹,Hong Guodong²,Fu Xiaolong³⁴,Wang Shengnan¹,Li Xinyu¹,Yang Haichao¹,Li Hongchen¹,Zhang Haiwei¹,Yang Yuxin¹,Xiao Jundan¹,Dong Hui⁵,Liu Yaling⁵,Shen Haitao⁶⁷,Lv Ping¹

Affiliation:

1. Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University Shijiazhuang Hebei China

2. Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China

3. Shandong Provincial Hospital, Medical Science and Technology Innovation Center, College of Clinical and Basic Medicine Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China

4. Department of Neurology, Aerospace Center Hospital, School of Life Science Beijing Institute of Technology Beijing China

5. Department of Neurology, The Second Hospital of Hebei Medical University, The Key Laboratory of Neurology, Ministry of Education Hebei Medical University, Neurological Laboratory of Hebei Province Shijiazhuang Hebei China

6. Lab of Pathology Hebei Medical University, Shijiazhuang Hebei China

7. Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation Affiliated Hospital of Hebei University Baoding Hebei China

Abstract

AbstractAge‐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 Cav1.3 calcium channel function in the inner hair cell (IHC) synapse in mice with AHL. IL‐6 upregulated the Cav1.3 channel via the Janus kinase‐mitogen activated kinase pathway, causing neurotransmitter excitotoxicity and synapse impairment; IL‐6 deficiency or the administration of a Cav1.3 channel blocker attenuated this age‐related damage, and rescued hearing loss. Thus, IL‐6‐dependent inflammaging upregulated the Cav1.3 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.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.14305

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