Willott J F, Erway L C, Archer J R, Harrison D E
Department of Psychology, Northern Illinois University, DeKalb 60115-2892, USA.
Hear Res. 1995 Aug;88(1-2):143-55. doi: 10.1016/0378-5955(95)00107-f.
The effects of genotype and diet on age-related hearing loss were evaluated using auditory brainstem response (ABR) thresholds and post-mortem cochlear histopathology in 5 inbred mouse strains, CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J (B6), BALB/cByJ (BY) and WB/ReJ (WB), and their 10 F1 hybrid strains. The mice had been maintained since weaning on either a high-energy (HE) control diet or low-energy (LE) calorically restricted diet. ABR thresholds were obtained when the mice were 23 months old; the mice were allowed to age until they died from natural causes 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 WB strains each possessed a different recessive allele causing age-related hearing loss, D2 mice possessed all 3 genes, and CH mice possessed none. The histopathology indicates that the genes act at the cochlear level. Dietary restriction resulted in increased longevity in a number of strains, but age-related changes in cochlear pathology were not ameliorated in any of these; indeed, in some strains long-lived LE mice exhibited severe cochlear degeneration. In strains for which longevity was not extended by caloric restriction, only B6 mice exhibited an ameliorative 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 hybrid strains.
利用听觉脑干反应（ABR）阈值和死后耳蜗组织病理学，在5个近交系小鼠品系CBA/H-T6J（CH）、DBA/2J（D2）、C57BL/6J（B6）、BALB/cByJ（BY）和WB/ReJ（WB）及其10个F1杂交品系中评估了基因型和饮食对年龄相关性听力损失的影响。这些小鼠自断奶后一直维持在高能量（HE）对照饮食或低能量（LE）热量限制饮食中。在小鼠23个月大时获得ABR阈值；在获取组织学材料之前，让小鼠自然老化直至死亡。食用HE饮食的小鼠死后耳蜗病理学的严重程度支持了我们早期的遗传模型，该模型假设B6、BY和WB品系各自拥有一个导致年龄相关性听力损失的不同隐性等位基因，D2小鼠拥有所有3个基因，而CH小鼠则一个都没有。组织病理学表明这些基因在耳蜗水平起作用。饮食限制导致许多品系的寿命延长，但耳蜗病理学的年龄相关性变化在任何一个品系中都没有得到改善；实际上，在一些品系中，长寿的LE小鼠表现出严重的耳蜗退化。在热量限制未延长寿命的品系中，只有B6小鼠表现出LE饮食对耳蜗病理学的改善作用。23个月大的小鼠的ABR表明，3个F1杂交品系的LE小鼠的年龄相关性听力损失有所减缓。
