Researchers have discovered a signaling pathway called mTORC2 that may play a key role in age-related hearing loss. When this pathway was inactivated in mice, their hearing began to decline, and by 12 weeks, they were completely deaf. Research shows that as we age, the production of important proteins in this signaling pathway decreases, which may lead to reduced synapses and function of auditory sensory cells, leading to hearing loss. This finding, if validated, could lay the foundation for future therapeutic interventions.
As they age, many people find themselves in need of hearing aids. In some cases, the reason may be that signaling pathways that control auditory sensory cell function are downregulated with age. Researchers at the University of Basel are looking for clues.
Almost everyone will experience hearing loss during their lifetime: Loud noises or regular aging gradually cause the auditory sensory cells and their synapses in the inner ear to degenerate and die. The only treatment is to wear a hearing aid or, in extreme cases, a cochlear implant.
Dr. Maurizio Cortada from the Department of Biomedicine at the University of Basel and University Hospital Basel explains: "In order to develop new treatments, we need to better understand the conditions required for auditory sensory cells to work properly."
Cortada collaborated with Professor Michael N. Hall's research group at the Biozentrum to study which signaling pathways influence the so-called sensory "hair cells" in the inner ear. Researchers report in the journal iScience that they have discovered a central regulator in this process.
This signaling pathway, called the mTORC2 signaling pathway by researchers, plays an important role in cell growth and cytoskeleton. Its role in inner ear hair cells has not been studied before.
When researchers removed a gene central to this signaling pathway in hair cells in the inner ears of mice, the mice gradually lost their hearing. By the time the mice were twelve weeks old, they were completely deaf, the authors report in the study.
A closer look revealed that sensory hair cells in the inner ear lost their sensors without the mTORC2 signaling pathway: Hair cells have projections similar to fine hairs that are important for converting sound into nerve signals. The researchers used electron microscopy to determine that these "fine hairs" were shortened. The number of synapses that transmit signals to the auditory nerve is also reduced.
"We know from other studies that the production of key proteins in this signaling pathway decreases as we age," Cortada explained. "There may be a link between the loss of synapses and the diminished function of auditory sensory cells in the inner ear, which contributes to hearing loss with age."
"If this is confirmed, it would be a possible starting point for future therapies," the researchers said. "For example, the middle and inner ears could readily be subject to topical administration or gene therapy. These results could pave the way for the development of such treatment options."