Pathology and mechanisms of cochlear aging

Keithley, Elizabeth M.

doi:10.1002/jnr.24439

Cited by 164 publications

(123 citation statements)

References 129 publications

(165 reference statements)

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“…As opposed to congenital hearing loss, acquired hearing loss results from a non-genetic, exogenous, or idiopathic etiology. The most common acquired cause of SNHL in adults is presbycusis, the loss of hearing that accompanies the aging process (Keithley, 2019;Fischer et al, 2020;Wang and Puel, 2020). Other acquired causes of hearing loss in adults include noise exposure, ototoxic medications, and vascular changes resulting from chronic conditions (Cunningham and Tucci, 2017;Liberman and Kujawa, 2017).…”

Section: And Acquired Hearing Lossmentioning

confidence: 99%

Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities

et al. 2020

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The use and utility of cochlear implantation has rapidly increased in recent years as technological advances in the field have expanded both the efficacy and eligible patient population for implantation. This review aims to serve as a general overview of the most common hearing disorders that have favorable auditory outcomes with cochlear implants (CI). Hearing loss in children caused by congenital cytomegalovirus infection, syndromic conditions including Pendred Syndrome, and non-syndromic genetic conditions such as hearing impairment associated with GJB2 mutations have shown to be successfully managed by CI. Furthermore, cochlear implantation provides the auditory rehabilitation for the most common etiology of hearing loss in adults and age-related hearing loss (ARHL) or presbycusis. However, in some cases, cochlear implantation have been associated with some challenges. Regarding implantation in children, studies have shown that sometimes parents seem to have unrealistic expectations regarding the ability of CI to provide auditory rehabilitation and speech improvement. Given the evidence revealing the beneficial effects of early intervention via CI in individuals with hearing disorders especially hearing loss due to genetic etiology, early auditory and genetic screening efforts may yield better clinical outcomes. There is a need to better understand genotype-phenotype correlations and CI outcome, so that effective genetic counseling and successful treatment strategies can be developed at the appropriate time for hearing impaired individuals.

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Section: And Acquired Hearing Lossmentioning

confidence: 99%

Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities

et al. 2020

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“…Heritability estimates for ARHL lie between 35% and 70% (Christensen, Frederiksen, Frederiksen, & Hoffman, 2001;Gates, Couropmitree, Couropmitree, & Myers, 1999;Hendrickx et al, 2013;Raynor et al, 2009) and noise exposure is a major environmental component that is difficult to separate from the underlying genetic basis (Liberman, 2017;Van Eyken, Van Camp, & Van Laer, 2007). Studies in aged animals and human temporal bones have given great insight into the histological deficit with degenerative changes in the sensory hair cells, the spiral ganglion neurons, and the stria vascularis predominantly described; Figure 1 (Keithley, 2019;Ohlemiller, 2004;Schuknecht, 1964;Schuknecht & Gacek, 1993).…”

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confidence: 99%

Age‐related hearing loss: Why we need to think about sex as a biological variable

Nolan

2020

J of Neuroscience Research

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It has long been known that age‐related hearing loss (ARHL) is more common, more severe, and with an earlier onset in men compared to women. Even in the absence of confounding factors such as noise exposure, these sexdifferences in susceptibility to ARHL remain. In the last decade, insight into the pleiotrophic nature by which estrogen signaling can impact multiple signaling mechanisms to mediate downstream changes in gene expression and/or elicit rapid changes in cellular function has rapidly gathered pace, and a role for estrogen signaling in the biological pathways that confer neuroprotection is becoming undeniable. Here I review the evidence why we need to consider sex as a biological variable (SABV) when investigating the etiology of ARHL. Loss of auditory function with aging is frequency‐specific and modulated by SABV. Evidence also suggests that differences in cochlear physiology between women and men are already present from birth. Understanding the molecular basis of these sex differences in ARHL will accelerate the development of precision medicine therapies for ARHL.

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“…Stereociliary defects, mitochondrial abnormalities or altered cellular metabolism observed in DFNA15 deafness mice are also reported in hearing loss caused by noise, aging and ototoxicity [ 59 – 62 ]. Therefore, upregulation of Pou4f3 by DEAB or other RA antagonists (e.g.…”

Section: Discussionmentioning

confidence: 99%

Aldh inhibitor restores auditory function in a mouse model of human deafness

Zhu

Gong

et al. 2020

PLoS Genet

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Genetic hearing loss is a common health problem with no effective therapy currently available. DFNA15, caused by mutations of the transcription factor POU4F3, is one of the most common forms of autosomal dominant non-syndromic deafness. In this study, we established a novel mouse model of the human DFNA15 deafness, with a Pou4f3 gene mutation (Pou4f3Δ) identical to that found in a familial case of DFNA15. The Pou4f3(Δ/+) mice suffered progressive deafness in a similar manner to the DFNA15 patients. Hair cells in the Pou4f3(Δ/+) cochlea displayed significant stereociliary and mitochondrial pathologies, with apparent loss of outer hair cells. Progression of hearing and outer hair cell loss of the Pou4f3(Δ/+) mice was significantly modified by other genetic and environmental factors. Using Pou4f3(-/+) heterozygous knockout mice, we also showed that DFNA15 is likely caused by haploinsufficiency of the Pou4f3 gene. Importantly, inhibition of retinoic acid signaling by the aldehyde dehydrogenase (Aldh) and retinoic acid receptor inhibitors promoted Pou4f3 expression in the cochlear tissue and suppressed the progression of hearing loss in the mutant mice. These data demonstrate Pou4f3 haploinsufficiency as the main underlying cause of human DFNA15 deafness and highlight the therapeutic potential of Aldh inhibitors for treatment of progressive hearing loss.

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Pathology and mechanisms of cochlear aging

Cited by 164 publications

References 129 publications

Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities

Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities

Age‐related hearing loss: Why we need to think about sex as a biological variable

Aldh inhibitor restores auditory function in a mouse model of human deafness

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