Aging Alters Hair Cell Physiological Properties in Mice With Late‐Onset Age‐Related Hearing Loss

Abstract

Cochlear hair cells convert sound stimuli into electrical signals. Age-related hearing loss (ARHL) is characterized by the progressive reduction of these hair cells and their synapses, but the underlying mechanisms remain poorly understood. In this study, we tested the hypothesis that hair cell function declines with age in CBA/CaJ mice, a strain known for its very slow ARHL progression. We found that hair cell size began to decrease from 10 months of age, before hearing loss was detectable. This structural change was associated with a significant decrease in the total current response and a distinct reduction in the expression of large conductance calcium-activated potassium (BK) channel currents (IK,f). However, the magnitude of the mechanoelectrical transducer (MET) currents at the hair cell stereociliary bundles remained unaffected. This observation challenges the common conception that stereocilia are the most fragile component of sensory cells in aging. Our results provide clear evidence of an early decline in hair cell function with age, which precedes measurable hearing loss, suggesting that these cellular deficits define a distinct pathological route to ARHL in the CBA/CaJ mouse model.