Comparative Cochlear-Vestibular Aging Reveals Age-Aligned Mitochondrial Ultrastructural Burden, Mitophagy-Autophagy Remodeling, Synaptic Uncoupling, and Sensory Functional Decline.

Jingyi Xie, Xujia Zhang, Jinyi Tian, Yulu Yan, Ke Shi, Yongqi Pan, Yanni Zhang, Zichen Chen, Jianbin Sun, Hui Lv, Jingguo Chen, Xiaoyong Ren, Teru Kamogashira, Xiaotong Zhang, Ying Gao

The Second Affiliated Hospital of Xi'an Jiaotong University, Department of Otorhinolaryngology-Head and Neck Surgery, Xi'an, China.The Second Affiliated Hospital of Xi'an Jiaotong University, Department of Otorhinolaryngology-Head and Neck Surgery, Xi'an, China. · pubmed

Paper

Abstract

Age-related hearing loss and balance decline are prevalent features of organismal aging, yet how the cochlea and vestibular organs converge on shared cellular liabilities remains insufficiently resolved. In particular, whether mitochondrial ultrastructural injury and mitochondrial quality-control programs co-vary with synaptic vulnerability and sensory functional decline across these systems within an age-resolved framework has not been clearly delineated. Here, we compared cochlear and vestibular aging in SAMP8 mice of different ages using integrated functional assays, region-resolved quantification of hair cells and CtBP2/GluA2 synapses, cochlear NF200+ fiber area fraction, transmission electron microscopy, and targeted qPCR of mitophagy/autophagy-lysosome genes. The results show that ABR thresholds rose progressively across 5.6-32 kHz. VsEP exhibited age-dependent threshold shifts and prolonged P-wave latency. Relative to the magnitude of synaptic and functional changes, cochlear hair-cell numbers were broadly preserved, although regional OHC loss was observed in middle-to-basal turns, whereas vestibular macular hair-cell density declined with age. Ultrastructurally, the proportion of pathological mitochondria increased with age, featuring electron-lucent matrix, disrupted cristae organization, and rounded/swollen profiles. What's more, guided by an adult-versus-aged transcriptomic screen nominating the Ca

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Research summary

This study characterizes the parallel mitochondrial and synaptic decline in the cochlea and vestibular system during aging in SAMP8 mice, providing descriptive mechanistic insights into age-related sensory loss. The research is relevant as it addresses fundamental cellular aging processes (mitochondrial quality control and synaptic integrity) in a specific tissue context, offering potential biomarkers or targets for age-related sensory decline, though it remains an incremental observational study rather than a transformative intervention.

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