DNA Damage Mechanisms Underpinning Age-Related and Noise-Induced Hearing Loss in Mice

Age-related hearing loss (ARHL) and noise-induced hearing loss (NIHL) are highly prevalent forms of hearing loss that can result in poor mental wellbeing. Hearing aids and cochlear implants are currently used to manage the hearing loss, however, these treatments are not best-suited for ARHL and NIHL patients, as they do not influence the underlying mechanisms behind the hearing loss. In order to develop new therapeutic strategies, and prevent the onset of ARHL/NIHL in the first place, the underlying disease mechanisms behind these forms of hearing need to be better understood.

One proposed mechanism is that excessive DNA damage within a cell’s nucleus can lead to the pathophysiological changes observed in ARHL and NIHL. To test this hypothesis, I performed immunohistochemistry of aged and noise-exposed cochleae from C57Bl/6N mice, in hope of identifying correlations between DNA damage levels and ARHL/NIHL.

Then, to identify whether manipulation of DNA damage/repair influenced susceptibility to
ARHL/NIHL, I recorded auditory brainstem responses (ABRs), both during ageing and following loud noise in mice with isolated mutations to two different DNA repair genes – Aptx and Atm – and a DNA damage-associated gene – Top1.

Taken together, these investigations shed more light on how DNA damage and repair impacts the function of cells within the organ of Corti, and raises questions for future investigation.