Vitamin D-deficient diet rescues hearing loss in Klotho mice

Abstract

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 14e18 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 1a-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.