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.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39148148.
- Also identified by DOI 10.1111/acel.14305 and PMC identifier 11634703.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>v</sub>1.3 calcium channel function in the inner hair cell (IHC) synapse in mice with AHL. IL-6 upregulated the Ca<sub>v</sub>1.3 channel via the Janus kinase-mitogen activated kinase pathway, causing neurotransmitter excitotoxicity and synapse impairment; IL-6 deficiency or the administration of a Ca<sub>v</sub>1.3 channel blocker attenuated this age-related damage, and rescued hearing loss. Thus, IL-6-dependent inflammaging upregulated the Ca<sub>v</sub>1.3 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.
Medical subject headings
- Up-Regulation
- Interleukin-6
- Hair Cells, Auditory, Inner
- Calcium Channels, L-Type