1. Academic Validation
  2. Upregulation of the Cav1.3 channel in inner hair cells by interleukin 6-dependent inflammaging contributes to age-related hearing loss

Upregulation of the Cav1.3 channel in inner hair cells by interleukin 6-dependent inflammaging contributes to age-related hearing loss

  • Aging Cell. 2024 Aug 15:e14305. doi: 10.1111/acel.14305.
Mingshun Lu 1 Fuyu Xian 1 Xishuo Jin 1 Guodong Hong 2 Xiaolong Fu 3 4 Shengnan Wang 1 Xinyu Li 1 Haichao Yang 1 Hongchen Li 1 Haiwei Zhang 1 Yuxin Yang 1 Jundan Xiao 1 Hui Dong 5 Yaling Liu 5 Haitao Shen 6 7 Ping Lv 1
Affiliations

Affiliations

  • 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

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 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.

Keywords

Cav1.3 channel; age‐related hearing loss; hair cells; interleukin 6.

Figures
Products