Vitamin D-deficient diet rescues hearing loss in Klotho mice

Klotho-deficient mice exhibit a premature aging syndrome, a feature of which is mild hearing loss. In the present study, the hearing phenotype of Klotho mice was characterized to better determine how well this phenotype resembles presbycusis in humans. It was demonstrated that Klotho animals have auditory-evoked brainstem response (ABR) threshold shifts of 14–18 dB in response to pure tone stimuli of 4, 8, 16 and 32 kHz, and similarly, in response to clicks; however, cochlear histology and spiral ganglion neuron density appeared normal in these mice. It was further demonstrated that a vitamin D-deficient diet normalizes serum calcitriol (1,25(OH)2D3) levels and prevents hearing loss in Klotho mice. It is concluded that hearing loss in Klotho mice is caused by elevated renal 1α-hydroxylase expression and consequent excessive production of calcitriol. These findings implicate the vitamin D metabolic pathway in hearing loss and pose questions as to the mechanism by which elevated calcitriol levels mediate such hearing loss.

► Klotho mice have hypervitaminosis D and mild hearing loss. ► Vitamin D-deficient diet was previously shown to rescue morbidity and mortality in Klotho mice. ► We showed that Vitamin D-deficient diet also rescues hearing loss. ► Klotho hearing loss is not associated with abnormality in cochlear hair cells or spiral ganglion neurons.