Age-related Hearing Loss Research Articles

Age-Related Hearing Loss: A cross-sectional study of healthy older Australians.

Introduction Hearing loss is common in ageing populations, but thorough investigation of factors associated with objective hearing loss in otherwise healthy, community dwelling older individuals is rare. We examined prevalence of age-related hearing loss (ARHL) in healthy, community-dwelling older adults, and determined whether sociodemographic, lifestyle or health factors associate with hearing thresholds. Audiometry assessment was investigated with self-reports of hearing loss and hearing handicap. Methods Australian participants (n=1260) of median age 73 years (IQR 71-76) joined ASPREE-Hearing, a sub-study of the ASPREE (ASPirin in Reducing Events in the Elderly) trial with exclusions including cognitive impairment, cardiovascular disease (CVD), independence-limiting physical disability, and uncontrolled hypertension. ASPREE collected demographics, anthropometrics, lifestyle, and health data. Audiometry measured better ear pure-tone-average (PTA) across four frequencies (0.5-4kHz) to establish hearing thresholds, categorised as normal or mild, moderate and severe hearing loss. Questionnaires collected perceived hearing problems and noise exposure. Results ARHL prevalence by audiometry was 49.7%, affecting men (59%) more than women (41%). A majority (54.5%) self-reported some hearing problems which mostly aligned with objective assessments; 45.6% self-reported a "little trouble" with hearing, while 35% had objective mild hearing loss; (8.3%) reported having a "lot of trouble" hearing while 13% had moderate hearing loss; and (0.6%) reported being "deaf" with 2% demonstrated severe hearing loss. There was a significant association (p<0.001) between self-reported hearing handicap and audiometric measures of hearing loss. In multivariate analysis of health, demographics and lifestyle risk factors only age, gender (men), and education years (<12) remained associated (P<0.05) with hearing loss. Hearing thresholds were not associated with smoking, living situation, alcohol use, hypertension, diabetes, or chronic kidney disease. Conclusion ARHL robustly assessed by audiometry is common among healthy older Australians with men more likely to have abnormal hearing thresholds than women. Hearing loss was associated with fewer years of formal education, but not with a range of chronic conditions or alcohol use. Self-reported hearing loss correlates well with higher PTA hearing threshold levels in this healthy cohort where prevalence was lower than previously reported for the age group >70 years. Hearing health education remains an important public health tool for this age. Targeting hearing in older patient health checks could be beneficial to mitigate the cognitive, social, and mental health consequences of ARHL, even if patients do not report a problem or handicap.

Realistic dual-task listening-while-balancing in older adults with normal hearing and hearing loss with and without hearing aids

Age-related hearing loss is a risk factor for mobility problems and falls, possibly due to poor access to spatial sounds or the higher allocation of attention required to listen, thereby reducing cognitive resources to support mobility. Introducing stabilizing spatial sounds or reducing cognitive load through hearing aids could possibly improve balance performance; however, evidence is mixed. Few studies have evaluated the effects of hearing aids and spatial sounds on balance during realistic, multisensory, dual-tasking conditions. This study used virtual reality to simulate a listening-while-balancing task in 22 older adults with normal hearing and 22 hearing aid users, tested with their aids on versus off. Participants performed a competing digits listening task (two, four digits) and a standing postural task, alone and in combination (dual task) under different visual, postural, and acoustical loads. Listening accuracy and postural outcomes (centre of pressure mean velocity, anterior–posterior standard deviation, medial–lateral standard deviation) were collected. With respect to listening accuracy, as expected, normal hearing adults had higher listening accuracy than those with hearing loss (aided better than unaided) and both groups performed better with eyes closed (vs. open) and under lower postural loads (firm vs. compliant). With respect to postural performance, hearing aids did not remarkably improve balance overall, with no effects on dual-task costs to posture. Other factors related to the complexity of the conditions (i.e., listening, visual, postural demands) differently influenced dual-task costs to posture in individuals with and without hearing loss. Overall, these results contribute to our understanding of how age-related hearing loss and hearing aids affect balance-related outcomes under realistic, complex, multisensory, multitasking conditions.

Vitamin C ameliorates D-galactose-induced senescence in HEI-OC1 cells by inhibiting the ROS/NF-κB pathway.

Cochlear hair cell senescence is one of the major causes of age-related hearing loss (ARHL) and is significantly related to reactive oxygen species (ROS) accumulation. Research shows that vitamin C (VC) can inhibit ROS accumulation; however, its association with cochlear hair cell senescence remains elusive. Firstly, a cellular senescence model was established using D-galactose (D-gal) induced HEI-OC1 cells for 24 h. Senescent HEI-OC1 cells were then continued to be treated with the addition of VC or ROS inhibitor (N-acetylcysteine; NAC) for another 24 h, and explored the impact of VC on senescent cochlear hair cell and the potential regulatory mechanisms. The results indicated that D-gal-induced senescent HEI-OC1 cells, manifested as decreased cell viability, increased β-galactosidase activity and p21 protein level, and ROS and pro-inflammatory factors were upregulated, and NF-κB p65 phosphorylation was enhanced. However, the use of VC or NAC can significantly ameliorate these effects and improve HEI-OC1 cell senescence. This research indicates that VC can ameliorate D-gal-induced senescence of HEI-OC1 cochlear hair cells, and its protective effect may be related to the inhibition of the ROS/NF-κB pathway, which provides a new research direction for the prevention and treatment of ARHL.

Study in murine model: Is there a relationship between presbycusis and frailty?

Age-related hearing loss (ARHL) or Presbycusis is the most frequent sensory deficiency in older adults and is associated with comorbidities, such as falls, cognitive decline, and frailty. Frailty is related to poor health outcomes in old age. Recent research suggested that ARHL may be a potentially modifiable risk factor for frailty, although inconclusive. The use of animal models to study the correlation between ARHL and frailty is important to test future interventions to be translated into clinical practice. The aim of this study was to determine if there is an association between ARHL and frailty in experimental animals based on the human frailty phenotype. This research studied male and female C57Bl/6J mice, at different ages (6, 14, and 22 months). Auditory steady-state responses (ASSR) threshold shifts were measured at different frequencies. To assess frailty status, we were based on the "Valence Score" which consists of measuring: weakness, weight loss, low level of activity, slowness, and little resistance. We found that hearing is significantly lower in older age groups. The mice become frail as they age. The worsening in ASSR threshold shifts with age correlates significantly with an increasing frailty. No significant differences were found between both sexes. Our research is, to our knowledge, the first carried out in experimental animals to establish the association between ARHL and frailty, which would provide a useful tool to evaluate future interventions in mice before translating them into clinical practice.

The role of cochlea extracellular matrix in age-related hearing loss.

Age-related hearing loss (ARHL) is a common disease among the elderly. Although its pathogenesis remains unclear by now, it is widely accepted that ARHL is associated with the degenerative alterations within each component of the cochlea. Extracellular matrix (ECM) plays a crucial role in cochlear structure and function, providing not only structural support but also participating in vital physiological processes including the development, differentiation, survival of auditory sensory cells, and sound perception. ECM is implicated in the pathogenesis of various neurodegenerative diseases, with certain ECM proteins or associated molecules emerging as potential therapeutic targets. However, few research were carried out on ECM in the cochlea and ECM associated molecules in ARHL. This review aims to delineate the composition of ECM in the cochlea, the changes of the main ECM structure in the cochlea such as the tectorial membrane (TM), the basilar membrane (BM) and the spiral ligament (SL) during aging, as well as the role of ECM associated molecules in ARHL. We hope that this review will foster further research into ARHL.

Polygenic Risk Scores and Hearing Loss Phenotypes in Children

Monogenic causes of childhood hearing loss are well established, as are polygenic risk contributions to age-related hearing loss. However, an untested possibility is that polygenic risk scores (PRS) also contribute to childhood hearing loss of all severities, alongside environmental and/or monogenic causes. To examine the association between a PRS for adult hearing loss and childhood hearing loss phenotypes. This cross-sectional study used a unique population-based dataset spanning normal hearing to profound loss, combining 2 contemporaneous population cohorts in Australia. This included the Child Health CheckPoint, a national population-based cross-sectional study nested within the Longitudinal Study of Australian Children, and the Victorian Childhood Hearing Longitudinal Databank (VicCHILD), a statewide population-based longitudinal data bank open to every child with congenital hearing loss in Victoria, Australia. The analysis took place from March to August 2023. Genotype data were generated from saliva- or blood-derived DNA using global single-nucleotide variations arrays. Based on genotype data, PRS was computed using published UK Biobank genome-wide association study results for self-reported hearing difficulty in individuals aged 40 to 69 years. Hearing outcomes were classified by laterality (bilateral, unilateral), severity (mild, moderate, severe or worse) and types (sensorineural, conductive, mixed, auditory neuropathy, atresia). Analyses included multinominal logistic regressions of PRS with hearing outcomes. Overall, 1488 CheckPoint study children (49.8% boys, aged 11-12 years) and 527 VicCHILD study children (55.2% boys, aged 0-13 years) with hearing and genotype data were included. A 1-SD increment in PRS was associated with higher odds of mild (odds ratio [OR], 1.3; 95% CI, 1.0-1.6), moderate (OR, 5.1; 95% CI, 3.2-8.1), and severe or worse (OR, 5.3; 95% CI, 3.9-7.3) unilateral hearing loss compared with normal hearing. Similarly, the PRS was associated with increased odds of mild, moderate, and severe or worse bilateral hearing loss (per-SD ORs, 3.9-6.6) and all hearing loss types (per-SD ORs, 8.5-10.6). In this cross-sectional study, a PRS initially developed for adult hearing difficulty was associated with wide-ranging childhood hearing loss phenotypes, partly explaining hearing phenotype variations despite shared genetic and environmental factors (eg, preterm birth). Large-scale studies with objectively defined hearing phenotypes are crucial for refining PRS and predicting high-risk children.

Increased risk of falls in older adults with hearing loss and slow gait: results from the Otassha Study.

Age-related hearing loss (ARHL) and impaired gait both independently heighten the risk of accidental falls among older adults. However, the combined impact of these factors remains unclear. We analyzed the data of 786 community-dwelling Japanese older adults. Hearing was evaluated at frequencies of 1.0 and 4.0kHz, with participants categorized into ARHL (> 25dB) and non-ARHL groups. Gait was also assessed, defining slow gait (SG) as speeds one standard deviation below the age- and sex-specific mean. Participants were divided into four groups based on their ARHL and SG statuses and were monitored annually for 8years to track falls and related injuries. Throughout the follow-up, incidents included 328 single falls (9.6/100 person-years), 117 multiple falls (2.8/100 person-years), 249 minor injuries from falls (6.7/100 person-years), and 55 fractures due to falls (1.3/100 person-years). Cox proportional hazard regression models showed that participants without ARHL but with SG faced a significantly increased risk of frequent falls. Furthermore, ARHL combined with SG significantly raised the risk of both single and frequent falls, and increased the incidence of both minor and severe fall-related injuries, including fractures. In contrast, no significant association was found between ARHL alone and fall-related incidents. These findings suggest that the previously reported risk associated with hearing loss in fall incidents predominantly relates to gait impairment. The co-occurrence of ARHL and SG significantly escalates the risk of falls and related injuries, highlighting the critical need for routine gait monitoring.

Chronic Inflammation and Age-Related Hearing: Based on Mendelian Randomization.

Age-related hearing loss (ARHL) is a degenerative condition that involves both peripheral and central auditory system pathologies. There is a close relationship between chronic inflammation and ARHL, but there is currently a lack of in-depth exploration of this relationship, particularly regarding causality. Using age-appropriate mice for basic experiments to examine changes in central auditory nervous system inflammation, a cohort study was conducted to select relevant clinical data and observe inflammation changes in the elderly population with ARHL. Mendelian randomization was employed to investigate the causal relationship between chronic inflammation and ARHL. Clinical results indicate that CRP levels in the ARHL group are significantly higher than those in the normal group. Chronic inflammation also occurs in the auditory centers. Mendelian randomization studies provide causal evidence that genetic chronic inflammation factors do not increase the risk of ARHL. This article provides reliable causal evidence of the relationship between chronic inflammation and ARHL, confirming the accumulation of inflammatory factors in the auditory center, which provides a basis for the prevention and treatment of ARHL and has a good prevention prospect. However, due to the differences of research objects, this study has limitations and needs further research.

Resistance to age-related hearing loss in the echolocating big brown bat (Eptesicus fuscus).

Hearing mediates many behaviours critical for survival in echolocating bats, including foraging and navigation. Although most mammals are susceptible to progressive age-related hearing loss, the evolution of biosonar, which requires the ability to hear low-intensity echoes from outgoing sonar signals, may have selected against the development of hearing deficits in bats. Many echolocating bats exhibit exceptional longevity and rely on acoustic behaviours for survival to old age; however, relatively little is known about the ageing bat auditory system. In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats (Eptesicus fuscus) and measured hearing sensitivity in young and ageing bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in bats up to 12.5 years of age, demonstrated by comparable thresholds and similar ABR and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear ageing, with similar hair cell counts, afferent and efferent innervation patterns in young and ageing bats. Here, we demonstrate that big brown bats show minimal evidence for age-related hearing loss and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.

Age-related hearing loss and "hearables": An agenda for moral considerations.

Rapid advances in digital hearing technologies, also known as hearables, are expected to disrupt the direct-to-consumer health market. For older adults with higher incidence of hearing loss, such disruption could reduce hearing problems, increase accessibility to hearing aids, and mitigate related stigmas. This paper delves into the intersection of disruptive innovation and hearables within the realm of biomedical ethics. Through a comprehensive exploration, we shed light on the ethical implications surrounding hearables. By critically evaluating the key ethical advantages and drawbacks, we find that no single concern presents an insurmountable a priori objection to hearables. We conclude with some ideas to maximize the benefits of hearables and further promote opportunities for equitable hearing health.

Exploring the cognitive effects of hearing loss in adult rats: Implications for visuospatial attention, social behavior, and prefrontal neural activity

Age-related hearing loss in humans has been associated with cognitive decline, though the underlying mechanisms remain unknown. We investigated the long-term effects of hearing loss on attention, impulse control, social interaction, and neural activity within medial prefrontal cortex (mPFC) subregions.Hearing loss was induced in adult rats via intracochlear neomycin injection (n = 13), with non-operated rats as controls (n = 10). Rats were tested for motor activity (open field), coordination (Rotarod), and social interaction (including ultrasonic vocalization, USV) before surgery and at weeks 1, 2, 4, 8, 16, and 24 post-surgery. From week 8 on, rats were trained in the five-choice serial reaction time task (5-CSRTT) to assess visuospatial attention and impulse control. Finally, oscillatory neuronal activity in mPFC subregions was recorded with multielectrode arrays during anesthesia, followed by immunohistological staining for NeuN+ and Parvalbumin+ cells.Deafened rats were more active than controls, whereas social interaction and USV were temporarily reduced. They also had difficulties to learn the concept of the 5-CSRTT paradigm and made more incorrect responses. Electrophysiology showed decreased power in theta, alpha, and beta frequency, and enhanced high gamma band in the mPFC in deafened rats, which was most pronounced in the cingulate subregion (Cg1). The number of NeuN+ and Parvalbumin+ cells, however, did not differ between groups.The behavioral deficits together with the altered neuronal activity found in the Cg1 subregion of the mPFC in adult deafened rats may be used as an endophenotype to elucidate the mechanisms behind the cognitive decline seen in older patients with hearing loss.

Spatial selective auditory attention is preserved in older age but is degraded by peripheral hearing loss

Interest in how ageing affects attention is long-standing, although interactions between sensory and attentional processing in older age are not fully understood. Here, we examined interactions between peripheral hearing and selective attention in a spatialised cocktail party listening paradigm, in which three talkers spoke different sentences simultaneously and participants were asked to report the sentence spoken by a talker at a particular location. By comparing a sample of older (N = 61; age = 55–80 years) and younger (N = 58; age = 18–35 years) adults, we show that, as a group, older adults benefit as much as younger adults from preparatory spatial attention. Although, for older adults, this benefit significantly reduces with greater age-related hearing loss. These results demonstrate that older adults with excellent hearing retain the ability to direct spatial selective attention, but this ability deteriorates, in a graded manner, with age-related hearing loss. Thus, reductions in spatial selective attention likely contribute to difficulties communicating in social settings for older adults with age-related hearing loss. Overall, these findings demonstrate a relationship between mild perceptual decline and attention in older age.

Morphological phenotyping of the aging cochlea in inbred C57BL/6N and outbred CD1 mouse strains.

Morphological mouse phenotyping plays a pivotal role in the translational setting and even more in the area of auditory research, where mouse is a central model organism due to the evolutionary genetic relationship and morpho-functional analogies with the human auditory system. However, some results obtained in murine models cannot be translated to humans due to the inadequate description of experimental conditions underlying poor reproducibility. We approach the characterization of the aging process of the mouse cochlea in animals up to 18 months of age belonging to two of the most used outbred (CD1) and inbred (C57BL/6N) strains. Striving to reduce any environmental variable we performed our study compliantly to the ARRIVE guidelines. We integrated instrumental data (auditory brainstem response test), with morphological analyses to correlate functional discrepancies to morphological changes and track the differences in the evolution of sensorineural hearing loss in the two strains. We featured the localization of Gipc3, Myosin VIIa, and TMC1 in hair cells of the Corti organ as well as NF 200 and the density of type I neuron in the spiral ganglion. We outlined age-related hearing loss (ARHL) in both strains, and a clear drop in the selected marker localization. However, in CD1 we detected a different trend allowing the identification of potential strain-specific mechanisms, namely an increase in myosin VIIa in 6 months aging mice in comparison to 2 months old animals. Our findings represent an asset to investigate the strain-dependent physiological trigger of ARHL providing new insights in the translational area.

OSBPL2 inhibition leads to apoptosis of cochlea hair cells in age-related hearing loss by inhibiting the AKT/FOXG1 signaling pathway.

Age-related hearing loss (AHL) is a prevalent and multifaceted condition that significantly impacts a substantial portion of the aging population. Oxysterol Binding Protein-like 2 (OSBPL2) has been identified as a causal gene for hearing loss. However, its role in AHL is still unclear. In this study, we investigated the effect of OSBPL2 on the survival of cochlea hair cells. To simulate AHL in vitro, hair cell-like inner ear cells (HEI-OC1) were exposed to H2O2 treatment. OSBPL2 expression was significantly increased in HEI-OC1 cells after H2O2 treatment. OSBPL2 knockdown augmented cell death and apoptosis in H2O2-induced HEI-OC1 cells. Besides, H2O2 treatment also led to the inactivation of the AKT and FOXG1 signaling pathways in HEI-OC1 cells. Mechanistically, OSBPL2 silencing reinforced the inactivation of the FOXG1 signaling pathway in H2O2-treated HEI-OC1 cells by inhibiting the AKT signaling pathway. Under H2O2 treatment, AKT inhibition by MK2206 augmented the apoptosis of HEI-OC1 cells; on the contrary, AKT activation by SC79 treatment partially rescued the apoptosis of OSBPL2-knockdown HEI-OC1 cells. In addition, FOXG1 silencing significantly reversed the effects of AKT activation on OSBPL2-knockdown HEI-OC1 cells. Moreover, OSBPL2 expression and the activation status of the AKT/FOXG1 signaling pathway were confirmed in the cochleae of young and old C57BL/6 mice. In conclusion, our study provides evidence that OSBPL2 inhibition sensitizes HEI-OC1 cells to H2O2-induced apoptosis via inactivation of the AKT/FOXG1 signaling pathway, suggesting that OSBPL2 acts as an important regulator in AHL.

Executive Function Associations With Audibility-Adjusted Speech Perception in Noise.

Speech recognition in noise is challenging for listeners and appears to require support from executive functions to focus attention on rapidly unfolding target speech, track misunderstanding, and sustain attention. The current study was designed to test the hypothesis that lower executive function abilities explain poorer speech recognition in noise, including among older participants with hearing loss who often exhibit diminished speech recognition in noise and cognitive abilities. A cross-sectional sample of 400 younger-to-older adult participants (19 to < 90 years of age) from the community-based Medical University of South CarolinaLongitudinal Cohort Study of Age-related Hearing Loss were administered tasks with executive control demands to assess individual variability in a card-sorting measure of set-shifting/performance monitoring, a dichotic listening measure of selective attention/working memory, sustained attention, and processing speed. Key word recognition in the high- and low-context speech perception-in-noise (SPIN) tests provided measures of speech recognition in noise. The SPIN scores were adjusted for audibility using the Articulation Index to characterize the impact of varied hearing sensitivity unrelated to reduced audibility on cognitive and speech recognition associations. Set-shifting, dichotic listening, and processing speed each explained unique and significant variance in audibility-adjusted, low-context SPIN scores (ps < .001), including after controlling for age, pure-tone threshold average (PTA), sex, and education level. The dichotic listening and processing speed effect sizes were significantly diminished when controlling for PTA, indicating that participants with poorer hearing sensitivity were also likely to have lower executive function and lower audibility-adjusted speech recognition. Poor set-shifting/performance monitoring, slow processing speed, and poor selective attention/working memory appeared to partially explain difficulties with speech recognition in noise after accounting for audibility. These results are consistent with the premise that distinct executive functions support speech recognition in noise.

New Quadratic Discriminant Analysis Algorithms for Correlated Audiometric Data.

Paired organs like eyes, ears, and lungs in humans exhibit similarities, and data from these organs often display remarkable correlations. Accounting for these correlations could enhance classification models used in predicting disease phenotypes. To our knowledge, there is limited, if any, literature addressing this topic, and existing methods do not exploit such correlations. For example, the conventional approach treats each ear as an independent observation when predicting audiometric phenotypes and is agnostic about the correlation of data from the two ears of the same person. This approach may lead to information loss and reduce the model performance. In response to this gap, particularly in the context of audiometric phenotype prediction, this paper proposes new quadratic discriminant analysis (QDA) algorithms that appropriately deal with the dependence between ears. We propose two-stage analysis strategies: (1) conducting data transformations to reduce data dimensionality before applying QDA; and (2) developing new QDA algorithms to partially utilize the dependence between phenotypes of two ears. We conducted simulation studies to compare different transformation methods and to assess the performance of different QDA algorithms. The empirical results suggested that the transformation may only be beneficial when the sample size is relatively small. Moreover, our proposed new QDA algorithms performed better than the conventional approach in both person-level and ear-level accuracy. As an illustration, we applied them to audiometric data from the Medical University of South Carolina Longitudinal Cohort Study of Age-related Hearing Loss. In addition, we developed an R package, PairQDA, to implement the proposed algorithms.

Impact of age-related hearing loss on decompensation of left DLPFC during speech perception in noise: a combined EEG-fNIRS study.

Understanding speech-in-noise is a significant challenge for individuals with age-related hearing loss (ARHL). Evidence suggests that increased activity in the frontal cortex compensates for impaired speech perception in healthy aging older adults. However, whether older adults with ARHL still show preserved compensatory function and the specific neural regulatory mechanisms underlying such compensation remains largely unclear. Here, by utilizing a synchronized EEG-fNIRS test, we investigated the neural oscillatory characteristics of the theta band and synchronous hemodynamic changes in the frontal cortex during a speech recognition task in noise. The study included healthy older adults (n = 26, aged 65.4 ± 2.8), those with mild hearing loss (n = 26, aged 66.3 ± 3.8), and those with moderate to severe hearing loss (n = 26, aged 67.5 ± 3.7). Results showed that, relative to healthy older adults, older adults with ARHL exhibited lower activation and weakened theta band neural oscillations in the left dorsolateral prefrontal cortex (DLPFC) under noisy conditions, and this decreased activity correlated with high-frequency hearing loss. Meanwhile, we found that the connectivity of the frontoparietal network was significantly reduced, which might depress the top-down articulatory prediction function affecting speech recognition performance in ARHL older adults. The results suggested that healthy aging older adults might exhibit compensatory attentional resource recruitment through a top-down auditory-motor integration mechanism. In comparison, older adults with ARHL reflected decompensation of the left DLPFC involving the frontoparietal integration network during speech recognition tasks in noise.

A primate model animal revealed the inter-species differences and similarities in the subtype specifications of the spiral ganglion neurons

Type I spiral ganglion neurons are peripheral neurons essential for hearing perception. While they can be subdivided in mice based on characteristic gene expression patterns, detailed examinations of these subtypes in primates and humans are lacking. In this study, we investigated the developmental subtypes of spiral ganglion neurons in the common marmoset (Callithrix jacchus). We confirmed that Type I spiral ganglion can be divided based on the characteristic gene expression patterns of several marker genes. However, some combinations of these genes differ from those in rodents, suggesting common marmoset's suitability for advancing our understanding of human cochlear development. Additionally, identifying the essential time points for subtype specifications and subsequent maturation will aid in studying the primate-specific developmental biology of the inner ear. This could lead to new treatment strategies for hearing loss in humans and be valuable for studying age-related hearing loss, as well as designing regenerative therapies.

Impact of hearing rehabilitation programs on presbycusis management: a systematic review and meta-analysis of randomized controlled trials.

In the field of audiology, numerous studies have sought to understand and improve hearing rehabilitation programs for older adults afflicted with presbycusis. Despite this, the field lacks uniform standards pertaining to the intervention methods, frequency, and duration of such programs. These discrepancies have led to varying test results and inconsistent findings across multiple studies. This meta-analysis aimed to evaluate the efficacy of hearing rehabilitation programs in enhancing the utilization of hearing aids among older adults with presbycusis. We conducted a comprehensive exploration of PubMed, Embase, Cochrane Library, and Web of Science to identify randomized controlled trials assessing the role of hearing rehabilitation programs for patients with age-related hearing loss. The search period spanned from the inception of each database to September 12, 2024. Outcomes were synthesized using RevMan 5.4 software. Eight studies met the inclusion criteria, involving 598 patients (290 in the intervention group and 308 in the control group). It was observed that hearing rehabilitation programs significantly diminished self-perceived hearing impairment [MD = -5.80, 95% CI = (-8.16, -3.44), p < 0.00001] and negative emotional states [MD = -1.66, 95% CI = (-3.02, -0.29), p = 0.02], while enhancing hearing aid utilization [MD = 0.22, 95% CI = (0.08, 0.36), p = 0.002]. Nonetheless, these programs did not significantly augment patients' satisfaction with their hearing aids [MD = 0.09, 95% CI = (-0.17, 0.26), p = 0.66]. Hearing rehabilitation programs significantly improve hearing aid outcomes, reduce self-perceived hearing impairment, and alleviate negative emotional states in patients. However, the current body of evidence is insufficient to conclusively indicate that these programs enhance patient satisfaction with daily hearing aid usage.

Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation.

Traditional Chinese medicine (TCM) formulas, including the Er-Long-Zuo-Ci pill, Tong-Qiao-Er-Long pill, and Er-Long pill, have long been utilized in China for managing age-related hearing loss (ARHL). However, the specific bioactive compounds, pharmacological targets, and underlying mechanisms remain elusive. This study aims to find the shared bioactive ingredients among these three formulas, uncover the molecular pathways they regulate, and identify potential therapeutic targets for ARHL. Furthermore, it seeks to validate the efficacy of these major components through both in vivo and in vitro experiments. Common bioactive ingredients were extracted from the TCMSP database, and their putative target proteins were predicted using the Swiss Target Prediction database. ARHL-related target proteins were collected from GeneCards and OMIM databases. Our approach involved constructing drug-target networks and drug-disease-specific protein-protein interaction networks and conducting clustering, topological property analyses, and functional annotation through GO and KEGG enrichment analysis. Molecular docking analysis was utilized to delineate interaction mechanisms between major bioactive ingredients and key target proteins. Finally, in vivo and in vitro experiments involving ABR recording, immunofluorescent staining, HE staining, and quantitative PCR were conducted to validate the treatment effects of flavonoids on the declining auditory function in DBA/2J mice. We identified 11 common chemical compounds across the three formulas and their associated 276 putative targets. Additionally, 3350 ARHL-related targets were compiled. As an intersection of the putative targets of the common compounds and ARHL-related proteins, 145 shared targets were determined. Functional enrichment analysis indicated that these compounds may modulate various biological processes, including cell proliferation, apoptosis, inflammatory response, and synaptic connections. Notably, potential targets such as TNFα, MAPK1, SRC, AKT, EGFR, ESR1, and AR were implicated. Flavonoids emerged as major bioactive components against ARHL based on target numbers, with molecular docking demonstrating diverse interaction models between these flavonoids and protein targets. Furthermore, baicalin could mitigate the age-related cochlear damage and hearing loss of DBA/2J mice through its multi-target and multi-pathway mechanism, involving anti-inflammation, modulation of sex hormone-related pathways, and activation of potassium channels. This study offers an integrated network pharmacology approach, validated by in vivo and in vitro experiments, shedding light on the potential mechanisms, major active components, and therapeutic targets of TCM formulas for treating ARHL.