Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-0506, United States; Dept. of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, United States; VA Ann Arbor Health System, United States.
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-0506, United States.
Hear Res. 2018 Dec;370:11-15. doi: 10.1016/j.heares.2018.09.003. Epub 2018 Sep 7.
Adding rapamycin or acarbose to diet at 9-10 months of age has been shown to significantly increase life span in both male and female UM-HET3 mice. The current study examined cochleae of male and female UM-HET3 mice at 22 months of age to determine if either treatment also influenced age-related loss of cochlear hair cells. A large loss of cochlear outer hair cells was observed at 22 months of age in untreated mice in both apical and basal halves of the cochlear spiral. Addition of acarbose to diet had no significant effect on the amount of outer hair cell loss at 22 months of age or in its pattern, with large loss in both apical and basal halves. The addition of rapamycin to diet, however, significantly reduced outer hair cell loss in the basal half of the cochlea at 22 months of age when compared to untreated mice. There was no significant difference between male and female mice in any of the conditions. Age-related outer hair cell loss in the apical cochlea precedes outer hair cell loss in the base in many mouse strains. The results of the present study suggest that rapamycin but not acarbose treatment can delay age-related loss of outer hair cells at doses at which each drug increases life span.
在 9-10 个月大时，在饮食中添加雷帕霉素或阿卡波糖已被证明可显著延长雄性和雌性 UM-HET3 小鼠的寿命。本研究检查了 22 个月大的雄性和雌性 UM-HET3 小鼠的耳蜗，以确定这两种治疗方法是否也会影响与年龄相关的耳蜗毛细胞损失。在未经治疗的小鼠中，在耳蜗螺旋的顶端和基部的一半，均观察到大量的耳蜗外毛细胞在 22 个月大时丢失。在 22 个月大时，饮食中添加阿卡波糖对外毛细胞丢失的数量或其模式均无显著影响，顶端和基部均有大量丢失。然而，与未经治疗的小鼠相比，饮食中添加雷帕霉素可显著减少 22 个月大时耳蜗基部的外毛细胞丢失。在任何情况下，雄性和雌性小鼠之间均无显著差异。在许多小鼠品系中，顶端耳蜗的年龄相关性外毛细胞损失先于基底的外毛细胞损失。本研究的结果表明，雷帕霉素治疗而非阿卡波糖治疗可以延迟与年龄相关的外毛细胞损失，而这两种药物均可延长寿命。
