GENETICS OF AGE-RELATED HEARING-LOSS IN MICE .2. STRAIN DIFFERENCES AND EFFECTS OF CALORIC RESTRICTION ON COCHLEAR PATHOLOGY AND EVOKED-RESPONSE THRESHOLDS

The effects of genotype and diet on age-related hearing loss were eval uated using auditory brainstem response (ABR) thresholds and post-mort em cochlear histopathology in 5 inbred mouse strains, CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J (B6), BALB/cByJ (BY) and WB/ReJ (WE), and their 10 F1 hybrid strains. The mice had been maintained since weaning on ei ther a high-energy (HE) control diet or low-energy (LE) calorically re stricted diet. ABR thresholds were obtained when the mice were 23 mont hs old; the mice were allowed to age until they died from natural caus es prior to obtaining the histological material. The severity of post- mortem cochlear pathology in mice maintained with the HE diet supports our earlier genetic model which postulated that B6, BY, and WE strain s each possessed a different recessive allele causing age-related hear ing loss, D2 mice possessed all 3 genes, and CH mice possessed none. T he histopathology indicates that the genes act at the cochlear level. Dietary restriction resulted in increased longevity in a number of str ains, but age-related changes in cochlear pathology were not ameliorat ed in any of these; indeed, in some strains long-lived LE mice exhibit ed severe cochlear degeneration. In strains for which longevity was no t extended by caloric restriction, only B6 mice exhibited an ameliorat ive effect of the LE diet on cochlear pathology. ABRs in 23-month-olds indicated a slowing of age-related hearing loss in LE mice of 3 F1 hy brid strains.