Time-Series Transcriptome Analysis of the Older Adult Mouse Cochlea After Noise-Induced Hearing Loss Reveals an Acute Immune Response and Recovery-Associated Pathways.

Noise-induced hearing loss (NIHL) affects approximately 5% of the global population, significantly impairing health-related quality of life, and is of particular interest in the aging population due to its association with an increased risk of cognitive decline. The pathophysiology of NIHL involves a complex interplay of damage to multiple cellular structures within the cochlea. While the pathophysiology of NIHL has been extensively studied in young mice, limited research exists on the molecular mechanisms underlying NIHL in older adult populations. This study provides the first insights into temporal differences in gene expression following noise exposure in older mice with an average age of 17 months. We exposed mice to broadband noise of 115 dB sound pressure level (SPL) for 2 h and conducted auditory testing before and after noise exposure to confirm the presence of NIHL. Cochleae were collected at 24 h, 72 h, and 1 week post exposure for RNA sequencing (RNA-seq). Pathway enrichment analysis using the Ingenuity Pathway Analysis (IPA) tool revealed distinct temporal patterns in the cochlear transcriptome. Acute inflammatory pathways were prominently activated at 24 h following noise exposure, while pathways associated with collagen degradation, hormone signaling, potassium channel activity, and GABA receptor activation peaked at 72 h or 1 week after noise exposure. These findings shed light on the age-specific molecular responses to acoustic trauma, largely consistent with previous experiments in younger mice, and highlight critical windows for cochlear damage and repair. Understanding these temporal patterns in older adults provides information for the development of targeted treatment strategies to mitigate NIHL and its associated risks.