New discoveries pave the way for hearing loss treatments

Researchers have identified a signaling pathway, called the mTORC2-signaling pathway, that may play an important role in age-related hearing loss. When this pathway was disabled in the mice, they began to lose their hearing, and by twelve weeks, they were completely deaf. The study suggests that the production of important proteins in this signaling pathway declines with age, leading to a decline in function of synapses and auditory sensory cells, leading to hearing loss. If verified, this finding could provide a foundation for future therapeutic interventions.

As they age, many people need hearing aids. In some cases, this may be due to a signaling pathway that regulates auditory sensory cell activity and slows down with age. Researchers at the University of Basel have found clues.

Almost everyone experiences hearing loss at some point in their lives: due to loud noises or simple aging, auditory sensory cells and their synapses gradually degenerate and die. The only treatment option is a hearing aid or, in extreme cases, a cochlear implant.

„To develop new therapies, we need to better understand what auditory sensory cells need for proper function,” explains Dr. Maurizio Cortada from the Department of Biomedicine at the University and University Hospital of Basel.

Fluorescence microscopic image of a murine cochlea

Fluorescence micrograph of a murine cochlea: hair cells are labeled in green, cell skeleton in red, and cell nuclei in blue with genetic material. Credit: Maurizio Cortada, University of Basel, Department of Biomedicine

Professor Michael N. at the BioCentrum. Together with Hall’s research team, Cortada investigated which signaling pathways affect the so-called sensory „hair cells” in the inner ear. In the process, the researchers discovered a central regulator, they report in the journal Science.

This signaling pathway, known to researchers as the mTORC2-signaling pathway, plays important roles in cell growth and the cytoskeleton, among other things. The role it plays in hair cells in the inner ear has not been studied before.

When the researchers removed a gene central to this signaling pathway in hair cells in the inner ear of mice, the animals gradually lost their hearing. By twelve weeks of age, they were completely deaf, the authors report in the study.

Fewer synchronicities

Closer examination indicated that without the mTORC2 signaling pathway, sensory hair cells in the inner ear have lost their sensors: hair cells have small hair-like protuberances that are important for transmitting sound to nerve signals. As the researchers determined using electron microscopes, these „tiny hairs” shrank. The number of synapses that send signals to the auditory nerve is also reduced.

„We know from other studies that the production of key proteins in this signaling pathway declines with age,” Cortada explains. There may be a link between loss of synapses and reduced function of auditory sensory cells in the inner ear, leading to hearing loss with age.

„If this is confirmed, it could be a starting point for future treatments,” says the researcher. For example, the middle and inner ear are readily accessible to locally administered drugs or gene therapies. The results could pave the way for the development of such treatment options.

Note: Mauricio Cortada, Soledad Levano, Michael N. Hall and Daniel Bodmer, 18 August 2023, “mTORC2 Regulates Auditory Hair Cell Structure and Function” Science.
DOI: 10.1016/j.isci.2023.107687

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