Abstract
Age-related hearing (ARHL) loss affects a large part of the human population with a major impact on our aging societies. Yet, underlying mechanisms are not understood, and no validated therapy or prevention exists. NADPH oxidases (NOX), are important sources of reactive oxygen species (ROS) in the cochlea and might therefore be involved in the pathogenesis of ARHL. Here we investigate ARHL in a mouse model. Wild type mice showed early loss of hearing and cochlear integrity, while animals deficient in the NOX subunit p22phox remained unaffected up to six months. Genes of the excitatory pathway were down-regulated in p22phox-deficient auditory neurons. Our results demonstrate that NOX activity leads to upregulation of genes of the excitatory pathway, to excitotoxic cochlear damage, and ultimately to ARHL. In the absence of functional NOXs, aging mice conserve hearing and cochlear morphology. Our study offers new insights into pathomechanisms and future therapeutic targets of ARHL.
Highlights
Presbycusis or age-related hearing loss is a frequent, degenerative neurosensory disorder in ageing societies
In order to characterize the early onset hearing loss in A/J mice, we investigated hearing thresholds starting over an age range from 4 to 26 weeks (Fig. 1A and B)
This was accompanied by a dramatic decrease in the number of synaptic ribbons per inner hair cell (IHC) (Fig. 1G–J) and a marked decrease in the neuronal density in the spiral ganglion with age (Fig. 1KN)
Summary
Presbycusis or age-related hearing loss is a frequent, degenerative neurosensory disorder in ageing societies. Presbycusis affects more than a third of the elderly population at retirement age [1] Hearing loss in this vulnerable population substantially contributes to cognitive decline, depression and social isolation [2,3] and represents an important socio-economic burden. Finding new treatments to reverse or slow down the progression of age-related hearing loss will have major consequences for the affected individuals and for society as a whole. The etiology of presbycusis is multifactorial and involves a complex interaction of genes. It can be triggered by a variety of external and internal factors such as noise exposure, ototoxic molecules and medical conditions, among others [4]. The typical age-related hearing loss is predominantly affecting the higher frequencies, which are coded at the cochlear base
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