Age-related hearing loss (or presbyacusis) is a progressive pathophysiological process. This study addressed the hypothesis that degeneration/dysfunction of multiple nonsensory cell types contributes to presbyacusis by evaluating tissues obtained from young and aged CBA/CaJ mouse ears and human temporal bones. Ultrastructural examination and transcriptomic analysis of mouse cochleas revealed age-dependent pathophysiological alterations in 3 types of neural crest-derived cells, namely intermediate cells in the stria vascularis, outer sulcus cells in the cochlear lateral wall, and satellite cells in the spiral ganglion. A significant decline in immunoreactivity for Kir4.1, an inwardly rectifying potassium channel, was seen in strial intermediate cells and outer sulcus cells in the ears of older mice. Age-dependent alterations in Kir4.1 immunostaining also were observed in satellite cells ensheathing spiral ganglion neurons. Expression alterations of Kir4.1 were observed in these same cell populations in the aged human cochlea. These results suggest that degeneration/dysfunction of neural crest-derived cells maybe an important contributing factor to both metabolic and neural forms of presbyacusis. (C) 2019 Elsevier Inc. All rights reserved.