Advances in understanding of presbycusis

Tawfik, Kareem O.; Klepper, Kristin; Saliba, Joe; Friedman, Rick A.

doi:10.1002/jnr.24426

Cited by 42 publications

(22 citation statements)

References 123 publications

(161 reference statements)

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“…Cochlear ion channels play a critical role in maintaining normal hearing. They are crucial for supporting hair cell development, maintaining the endocochlear potential (EP) and synaptic transmission (Tawfik et al, 2019;Fuchs, 1996). Many studies have identified plenty of mutations in membrane transport proteins which result in progressive hearing loss with age (Tawfik et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis highlights cochlear inflammation associated with age-related hearing loss in C57BL/6 mice using next generation sequencing

Xiong

Liu

et al. 2020

PeerJ

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Background In our aging society, age-related hearing loss (AHL) is the most common sensory disorder in old people. Much progress has been made in understanding the pathological process of AHL over the past few decades. However, the mechanism of cochlear degeneration during aging is still not fully understood. Methods Next generation sequencing technique was used to sequence the whole transcriptome of the cochlea of C57BL/6 mice, a mouse model of AHL. Differentially expressed genes (DEGs) were identified using the Cuffdiff software. GO and KEGG pathway enrichment analyses of the DEGs were implemented by using the GOseq R package and KOBAS software, respectively. Results A total of 731 genes (379 up- and 352 down-regulated) were revealed to be differentially expressed in the cochlea of aged mice compared to the young. Many genes associated with aging, apoptosis, necroptosis and particularly, inflammation were identified as being significantly modulated in the aged cochlea. GO and KEGG analyses of the upregulated DEGs revealed that the most enriched terms were associated with immune responses and inflammatory pathways, whereas many of the downregulated genes are involved in ion channel function and neuronal signaling. Real-time qPCR showed that H2O2 treatment significantly induced the expression of multiple inflammation and necroptosis-related genes in HEI-OC1 cells. Conclusion Using next generation sequencing, our transcriptomic analysis revealed the differences of gene expression pattern with age in the cochlea of C57BL/6 mice. Our study also revealed multiple immune and inflammatory transcriptomic changes during cochlear aging and provides new insights into the molecular mechanisms underlying cochlear inflammation in AHL.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis highlights cochlear inflammation associated with age-related hearing loss in C57BL/6 mice using next generation sequencing

Xiong

Liu

et al. 2020

PeerJ

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“…Presbycusis arises in the inner ear (Keithley, 2019;Tawfik et al, 2019;Fischer et al, 2020), where sound is transduced, by inner hair cells (IHCs), into electrical signals carried by auditory nerve fibers (ANFs) to the brain (Fig. 1A,C).…”

Section: Introductionmentioning

confidence: 99%

Age-Related Hearing Loss Is Dominated by Damage to Inner Ear Sensory Cells, Not the Cellular Battery That Powers Them

et al. 2020

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Age-related hearing loss arises from irreversible damage in the inner ear, where sound is transduced into electrical signals. Prior human studies suggested that sensory-cell loss is rarely the cause; correspondingly, animal work has implicated the stria vascularis, the cellular "battery" driving the amplification of sound by hair cell "motors." Here, quantitative microscopic analysis of hair cells, auditory nerve fibers, and strial tissues in 120 human inner ears obtained at autopsy, most of whom had recent audiograms in their medical records, shows that the degree of hearing loss is well predicted from the amount of hair cell loss and that inclusion of strial damage does not improve the prediction. Although many aging ears showed significant strial degeneration throughout the cochlea, our statistical models suggest that, by the time strial tissues are lost, hair cell death is so extensive that the loss of battery is no longer important to pure-tone thresholds and that audiogram slope is not diagnostic for strial degeneration. These data comprise the first quantitative survey of hair cell death in normal-aging human cochleas, and reveal unexpectedly severe hair cell loss in low-frequency cochlear regions, and dramatically greater loss in high-frequency regions than seen in any aging animal model. Comparison of normal-aging ears to an age-matched group with acoustic-overexposure history suggests that a lifetime of acoustic overexposure is to blame.

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“…Age-related hearing loss involves numerous risk factors ranging from genetics to lifestyle, with the underlying mechanisms remaining largely unknown. However, damage to the auditory receptors in the cochlea, namely the inner and outer hair cells (IHCs and OHCs) and their innervation, is likely to play a key role (Johnsson, 1974;Schuknecht & Gacek, 1993;Sergeyenko et al 2013;Tawfik et al 2019;Wu et al 2019;Jimenez et al 2020). Although we now have a better understanding of age-related changes in OHCs (Jeng et al 2020a) and IHC ribbon synapses (Jeng et al 2020b), very little is known about how the biophysical properties of IHCs and their efferent innervation are affected by cochlear ageing, which limits our understanding of how IHC function contributes to the progression of ARHL.…”

Section: Introductionmentioning

confidence: 99%

Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea

Jeng

Carlton

Johnson

et al. 2020

The Journal of Physiology

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Age-related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. r We compared age-related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. r The surface area of apical coil IHCs (9-12 kHz cochlear region) decreases by about 30-40% with age. r The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. r The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23 ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23-repaired mice (C57BL/6NTac Cdh23+), indicating that it could contribute to the different progression of hearing loss among mouse strains. r The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains.

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Advances in understanding of presbycusis

Cited by 42 publications

References 123 publications

Transcriptomic analysis highlights cochlear inflammation associated with age-related hearing loss in C57BL/6 mice using next generation sequencing

Transcriptomic analysis highlights cochlear inflammation associated with age-related hearing loss in C57BL/6 mice using next generation sequencing

Age-Related Hearing Loss Is Dominated by Damage to Inner Ear Sensory Cells, Not the Cellular Battery That Powers Them

Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea

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