Age-related neurodegeneration is strongly linked to chronic inflammation in brain tissue. Age-related hearing loss is a form of neurodegeneration, the loss of sensory hair cells in the inner ear, or the loss of the connections between those cells and the brain. Thus to find that markers of chronic inflammation in the inner ear correlate with progressive deafness is not too surprising. Ways to effectively reduce the chronic inflammation of aging should go a long way towards reducing the impact of aging on health. Senolytic therapies to remove senescent cells are the best of the present options, but more than this will be needed for complete control of inflammation in age-damaged tissues.
Age-related hearing loss (ARHL) is a major hearing impairment characterized by pathological changes in both the peripheral and central auditory systems. Low-grade inflammation was observed in the cochlea of deceased human subjects with ARHL and animal models of early onset ARHL, which suggests that inflammation contributes to the development of ARHL. However, it remains elusive how chronic inflammation progresses during normal aging in the cochlea, and especially the accompanying changes of neuroinflammation in the central auditory system.
To address this, we investigated chronic inflammation in both the cochlea and the cochlear nucleus (CN) of CBA/CaJ mice, an inbred mouse strain that undergoes normal aging and develops human, like-late-onset ARHL. Using immunohistochemistry, confocal microscopy, and quantitative image processing, we measured the accumulation and activation of macrophages in the cochlea and microglia in the CN using their shared markers: ionized calcium binding adaptor molecule 1 (Iba1) and CD68-a marker of phagocytic activity.
We found progressive increases in the area covered by Iba1-labeled macrophages and enhanced CD68 staining in the osseous spiral lamina of the cochlea that correlated with elevated ABR threshold across the lifespan. During the process, we further identified significant increases in microglial activation and C1q deposition in the CN, indicating increased neuroinflammation and complement activation in the central auditory system. Our study suggests that during normal aging, chronic inflammation occurs in both the peripheral and the central auditory system, which may contribute in coordination to the development of ARHL.