The auditory nerve glial transition zone is a unique microenvironment with age-related alterations in phagocytic activity and immune activation, where macrophages/microglia accumulate and phagocytose myelin debris—including normal-appearing myelin—in ways not observed in other auditory nerve regions.
RNA-sequencing of the aged auditory nerve revealed enrichment of neuroinflammation and myelin degeneration-related pathways.
Aging was associated with an increase in Iba1+ macrophages/microglia throughout the auditory nerve, with prominent accumulation at the glial transition zone (GTZ).
Aged AN GTZ macrophages/microglia expressed markers indicative of enhanced phagocytic activity and altered activation state, including CD206, Gal3, CD163, and Lamp1.
CD68+ cells were increased at the AN GTZ and in the central AN with aging.
Macrophages/microglia contained significantly more internalized myelin debris across all regions of the AN with aging, including myelin localized within Lamp1+ lysosomes.
Normal-appearing myelin was frequently observed within macrophages/microglia at the AN GTZ but not in peripheral or central regions of the AN.
Myelin debris within Iba1+ cells was also found in human auditory nerve tissue, consistent with mouse findings.
The AN GTZ, located within the cochlear modiolus, represents a unique biological niche where myelination shifts from Schwann cells (peripheral AN) to oligodendrocytes (central AN).
This research suggests that a specific anatomical location within the inner ear—called the glial transition zone (GTZ) of the auditory nerve—becomes a hotspot for immune activity as we age. The GTZ is where the type of insulating material (myelin) surrounding nerve fibers switches from one cell type to another, creating a biologically unique environment. Using advanced imaging techniques in aging mice and human tissue, the researchers found that immune cells called macrophages and microglia accumulate at this specific location with age, and that these cells show signs of being highly active in engulfing and breaking down myelin, the protective sheath around nerve fibers. One of the most striking findings was that at the GTZ—but nowhere else along the auditory nerve—immune cells appeared to be consuming myelin that still looked healthy and intact, not just damaged or degenerating myelin. This is significant because it suggests immune cells at this location may be actively stripping away functional myelin, potentially contributing to auditory nerve degeneration and age-related hearing loss. Supporting this, genetic analysis of aged auditory nerve tissue showed increased activity of genes related to inflammation and myelin breakdown. These immune cell changes and the presence of myelin debris inside immune cells were confirmed in human ear tissue as well, making the findings potentially relevant to human aging and hearing loss. This research matters because age-related hearing loss affects hundreds of millions of people worldwide, and the underlying nerve-level mechanisms are not well understood. These findings point to the GTZ as a specific vulnerable location where immune-myelin interactions may drive auditory nerve damage with aging. Understanding which types of immune cells are involved and whether their myelin-engulfing activity is harmful or helpful could open new avenues for developing targeted treatments to slow or prevent age-related hearing loss.
Payne S, Anderson H, Brown I, Chai J, Chen P, Yao H, et al.. (2026). The auditory nerve glial transition zone is a focal site of age-related immune-myelin interactions.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1757234