Molecular changes associated with biological aging of cochlear hair cells

Age-related hearing loss (ARHL) is a progressive sensorineural hearing loss that occurs as people get older. As many as 35% to 50% of the population aged between 65 and 75 have ARHL. Although age-related changes in the central auditory system can contribute to hearing impairment, degeneration of the mechanosensitive hair cells in the cochlea is the prevalent cause of ARHL. The molecular mechanisms of hair cell aging are largely unknown. To provide a comprehensive dataset of age-related genes and pathways in hair cells, we individually collected inner and outer hair cells, the two types of sensory receptor cells in the cochlea, from 9- and 26-month-old CBA/J mice and performed cell type-specific transcriptomic analysis. Our analysis showed a significant reduction of the expression of genes related to hair cell structure and function such as Tmc1, Kcnq4, Kcnj13, Slc7a14, Slc17a8, Chrna9/Chrna10, and Slc26a5. Our hair cell-specific transcriptome analysis provides a rich resource for mechanistic studies of biological aging of cochlear hair cells. Individual inner hair cells and outer hair cells were manually and separately collected from cochleae of CBA mice aged 9 and 26 months based on their morphology using the pipette-aspiration technique. Each sample represents a biological replicate including ~1,000 hair cells collected from cochleae of 6 - 18 mice (both male and female).年龄相关性听力损失（Age-related hearing loss, ARHL）是一种随年龄增长进展的进行性感音神经性听力损失。65至75岁人群中，多达35%至50%会罹患该疾病。尽管中枢听觉系统的年龄相关变化可导致听力损伤，但耳蜗内机械敏感性毛细胞的退行性变是年龄相关性听力损失的主要致病诱因。目前，毛细胞衰老的分子机制在很大程度上尚不明确。为构建毛细胞中年龄相关基因与通路的综合数据集，我们从9月龄和26月龄的CBA/J小鼠体内分别采集耳蜗内的两种感觉受体细胞——内毛细胞与外毛细胞，并开展了细胞类型特异性转录组分析。分析结果显示，与毛细胞结构和功能相关的基因（如Tmc1、Kcnq4、Kcnj13、Slc7a14、Slc17a8、Chrna9/Chrna10及Slc26a5）的表达量显著降低。本项毛细胞特异性转录组分析为耳蜗毛细胞生理性衰老的机制研究提供了丰富的研究资源。研究人员通过吸管抽吸技术，依据形态学特征，从9月龄和26月龄的CBA小鼠耳蜗中手动分离并单独采集内毛细胞与外毛细胞。每个样本为一个生物学重复，包含从6至18只（雌雄兼具）小鼠的耳蜗中收集的约1000个毛细胞。