The relationship between hearing and motor function as a function of aging is unclear. Therefore, we aimed to clarify the relationship between age-related hearing loss and locomotive syndrome. In total, 240 participants aged ≥40 years, whose hearing acuity and motor function had been measured, were included in this study. Patients with a hearing acuity of <35 dB and ≥35 dB were categorized into normal and low hearing acuity groups, respectively. Motor function was compared according to sex between the groups. Among men, those in the low hearing acuity group (51/100) were older, had a significantly slower walking speed, and had a higher prevalence of locomotive syndrome than those in the normal group. Among women, those in the low hearing group (14/140) were older and had a significantly slower gait speed than those in the normal group. The multivariate analysis showed that, in the low hearing acuity group, age and gait speed were risk factors in men, while age was the only risk factor in women. In conclusion, hearing loss was associated with walking speed. The association between hearing loss and locomotive syndrome was observed only in men. In the multivariate analysis, hearing loss was associated with walking speed only in men. Sensory organs have a significant role in motor function . TherefoHearing has been shown to have a significant effect on motor function . SeveralLocomotive syndrome (LS) is an important indicator of motor function . LS signTo our knowledge, no study has reported an association between auditory function and LS, an important assessment of motor function. Once these associations are clarified, an association between hearing and locomotor function can be established, and effective prevention and treatment methods for motor function decline can be considered. This could significantly reduce the number of people requiring assistance and care in their daily lives.The prevalence of hearing loss increases with age. Hearing loss begins in the 40s and is present in 50–80% of people in their 80s . It has Participants in the study voluntarily took part during municipally sponsored health screenings in the town of Yakumo in 2019. The town of Yakumo boasts a population of around 17,000 residents, with nearly 28% being 65 years or above. Unlike city regions, Yakumo’s population is prominently involved in farming and fishing activities. Health screenings have been a consistent event in Yakumo since 1982, with the health checks comprising optional bone health checks, functional physical evaluations, internal health checks, mental evaluations, and a general health quality assessment (SF-36) . For thiOf the 537 participants who underwent physical examination, 240 (100 men and 140 women) met the inclusion criteria . The stuAn otolaryngologist examined the ears, nose, and throat before conducting the hearing tests. The hearing levels were evaluated using an audiometer  in a quiet room. We measured the hearing levels bilaterally at 1 and 4 kHz. The World Health Organization defines “disabling” hearing loss as hearing loss greater than 35 decibels (dB) in the better-hearing ear . ParticiPhysical dimensions such as height, weight, BMI, and the muscle mass index for each extremity were gauged with the BIA method. The InBody 770 BIA machine from Inbody Co., Ltd., Seoul, the Republic of Korea, which identifies tissues by their electric resistance, was employed . The forThe utmost isometric force from the back’s extensor muscles represents back muscle power. This was gauged using a T.K.K. 5102 digital dynamometer from Takei Seisakusho, Tokyo, Japan, while the subject stood bending their lumbar at 30° and extending their knee. The average of two separate tests was noted, and the highest force for each test was taken into account .The speed of mobility was deduced from the time a participant needed to traverse a 10 m straight path at their quickest speed. Each participant was evaluated twice, and the average of these times was utilized for evaluation .The Gravicorder GW-5000 by Anima Co. Ltd., Japan, was employed to gather data on balance. Participants were instructed to stand at the apparatus’s midpoint with both feet touching for one minute, first with eyes open and then eyes shut. The tool uses force sensors to detect any immediate shifts in the pressure’s center point (COP). The evaluated outcomes comprised the full distance of COP movement and the average squared area covered by COP shifts. Data were registered at a frequency of 100 Hz . The metAs per the guidelines of the Japanese Orthopaedic Association (JOA), LS risk is gauged with three specific tests: a dual-step exam, a standing from seated test, and the GLFS-25 questionnaire ,19. ThesThe JOA-prescribed evaluations were executed as follows ,19. The GLFS-25 is an exhaustive self-assessment referring to the past 30 days. This questionnaire incorporates four pain-related questions, sixteen daily activity-related queries, three questions about societal interactions, and two mental health-related questions. The grading for each response ranges from no issues (0 points) to significant issues (4 points).2 (m2), SMI = appendicular skeletal muscle mass (kg)/height2 (m2).Height, weight, body mass index (BMI), and skeletal muscle mass index (SMI) measured by BIA  were used . The BMIThe LS stages were rated on a scale of 0, 1, and 2 ,19. In tt-test, and categorical variables were compared between groups L and N by the chi-square test. Analyses were performed separately for men and women. Logistic regression analysis was used to verify the presence of risk factors in the L group. Univariate analysis was performed with variables that showed a p-value < 0.05. Using SPSS Statistics software , a p-value < 0.05 was considered statistically significant.Continuous variables were compared between groups L and N by the Student’s The total number of participants was 240 ; 175 were in the N group and 65 in the L group .2. The mean back muscle strength was 113.1 ± 24.4 kg. The mean walking speed was 2.18 ± 0.38 m/s ; N: N/LS = 32/17, L: N/LS = 19/32; p = 0.006). No significant differences were found in other items   0.254, 95% CI: 0.067–0.96, p = 0.043)  1.076, 95% confidence interval (CI): 1.017–1.140, = 0.043) .2. The mean back muscle strength was 65.1 ± 58.6 kg. The mean walking speed was 1.99 ± 0.32 m/s . No significant differences were found for the other items   1.176, 95% CI: 1.066–1.296, = 0.001) .Several studies on motor function and hearing have reported that older adults with hearing impairment have increased functional disability, a decreased ability to perform ADL, and an increased risk of frailty ,4. HowevOlder adults with hearing loss tend to exhibit mobility impairments such as slow walking . In the In this study, an association was found between LS and hearing loss only in men. LS is defined as “a condition in which motor function is impaired due to motor impairment” and often requires long-term care services for the elderly . LS leadThe rate of hearing loss was higher in men . The reaIt has been previously reported that individuals with cardiovascular risk factors such as hypertension, diabetes, smoking, increased serum cholesterol, or a decreased estimated glomerular filtration rate are at risk of developing hearing impairment . PreviouThis study has several limitations. First, the participants were middle-aged and older adults living in relatively rural areas, many of whom engaged in farming and fishing. Thus, their lifestyle differs from those of adults in urban areas. Therefore, the results of this study reflect only results in a specific demographic population and its relevance to the broader population cannot be confirmed. Therefore, the results do not reliably suggest that a direct relationship exists between hearing loss and motor function. Furthermore, although the preliminary results showing an association between hearing loss and motor function were revealed by multivariate analysis, this is part of hypothesis generation, and we cannot ignore the possibility that these associations may have occurred by chance. In other words, our observations could be a type 1 error. Therefore, our results require additional, more rigorous studies to confirm the association between these variables. Second, they attended annual health checkups, suggesting that they may be more health-conscious than others. In addition, less than half (240) of the total 537 participants in 2019 received all of the required screening items this time, suggesting that only health-conscious people may have been considered. Third, the rate of hearing loss was 14 out of 140 women, which is a small number of cases, and should be examined and confirmed using a larger population in the future. Finally, this was a cross-sectional single-site study. Future longitudinal, multicenter studies are required to validate our findings.Hearing loss and motor function were compared in healthy participants using the community health examination data. Hearing loss was associated with walking speed. The association between hearing loss and LS was observed only in men. Additionally, in the multivariate analysis, hearing loss was associated with walking speed only in men.


The skin transmits affective signals that integrate into our social vocabulary. As the socio-affective aspects of touch are likely processed in the amygdala, we compare neural responses to social grooming and gentle airflow recorded from the amygdala and the primary somatosensory cortex of non-human primates. Neurons in the somatosensory cortex respond to both types of tactile stimuli. In the amygdala, however, neurons do not respond to individual grooming sweeps even though grooming elicits autonomic states indicative of positive affect. Instead, many show changes in baseline firing rates that persist throughout the grooming bout. Such baseline fluctuations are attributed to social context because the presence of the groomer alone can account for the observed changes in baseline activity. It appears, therefore, that during grooming, the amygdala stops responding to external inputs on a short timescale but remains responsive to social context (or the associated affective states) on longer time scales.  Martin et al. report that neurons in the amygdala of social touch recipients do not respond to individual grooming sweeps yet remain responsive to airflow stimuli applied to the same location. Baseline firing rates, however, are modulated by social context and may contribute to gating phasic responses in the amygdala. The groomer builds alliances and gains coalition support, tolerance at feeding sites, infant handling, and even a potential rise in the hierarchy.21 The recipient attains a physiological state marked by muscle relaxation, reduced anxiety and vigilance, enhanced vagal tone, and the release of oxytocin and endorphins that counter the effects of circulating glucocorticoids induced by previous stressors.25 Similar physiological benefits have been documented in humans who receive affective touch from bonded partners,28 and in macaques who are groomed by trusted human caregivers.29 These observations led to the prediction that neurons in the amygdala would respond differentially to grooming and to innocuous tactile stimuli delivered to the same areas of the skin.Grooming in macaques is the equivalent of social and affective touch in humans. Beyond its hygienic role, grooming maintains the social homeostasis of hierarchical societies32 although often integrated with other sensory modalities, task variables, actions required, and even abstract features such as behavioral context.33 This is likely a consequence of convergence of multiple circuits in the amygdala that process sensory, affective, social, and autonomic signals.36 By virtue of its connections, the amygdala is in an ideal position to extract the affective significance of tactile stimuli and to enlist autonomic effectors to generate the corresponding physiological states.37 Indeed, the human amygdala is activated by pleasant touch.40 The magnitude of this activation depends not only on the mechanical properties of the stimuli, the activation of C-tactile afferents,41 but also on the body part touched and the relationship between the recipient and the deliverer of tactile stimulation.40 Affective touch also enhances the functional connectivity of the amygdala with several other cortical areas, including the subdivision of medial prefrontal cortex43 involved in affective and social processes.44Electrophysiological studies in macaques have shown that the amygdala responds robustly to somatosensory stimulation,45). Airflow elicited robust responses from both areas. Surprisingly, however, episodic responses to grooming in the amygdala were absent. Furthermore, under different social contexts accompanied by disparate autonomic states, long-lasting modulation of baseline activity in the amygdala was observed. This suggests that the amygdala switches into different modes of sensory processing depending on the social situation. The transmutation of sensing to feeling, therefore, may not only depend on the type of skin mechanoreceptors activated by touch,1 but also on the instantiation of social context by the amygdala.Given the responsivity of the amygdala to tactile stimulation and its processing bias for stimuli with affective significance, we asked whether neurons in the amygdala would respond differentially to grooming and to an innocuous tactile stimulus. Specifically, we compared the tactile responses elicited by gentle airflow with responses elicited by grooming-like finger sweeps delivered by a trusted human trainer. We also recorded responses to these two forms of tactile stimuli at an early cortical processing stage in the primary somatosensory cortex  delivered through a set of adjustable nozzles directed to 10 distinct regions of the face plus a sham airflow directed away from the face . Our preBlocks of grooming alternated with blocks of airflow . For gro31We used two 32-channel V-probes to record neural responses to the two types of tactile stimuli in area 3b of the primary somatosensory cortex (SI) and from the amygdala simultaneously. Of the 315 neurons recorded in SI, 269 responded to at least one tactile stimulus. Of the 615 neurons recorded in the amygdala that had an average firing rate >1 Hz and were stable for a sufficient number of trials to assess stimulus responsiveness see , 333 res46 slight differences in the locations of airflow and grooming stimuli may partially account for the lower percentage than expected of neurons responding to both types of tactile stimuli. About 23% of neurons responded exclusively to airflow and another 24% to grooming sweeps applied to the face. Overall, 77% of tactile-responsive neurons in SI responded to grooming, while only 7% did so in the amygdala.Compared with neurons in SI, neurons in the amygdala exhibited a different pattern of responses to tactile stimuli. As shown in To establish that the observed difference between SI and the amygdala in response to grooming was not explained solely by differences in the mechanical properties of stimuli or other features of experimental design, we carried out five control experiments .First, we tested whether suppressed responses to grooming were due to inadequate stimulus pressure. To do this, we measured neural responses in the amygdala and SI to grooming stimuli that were approximately doubled and halved in magnitude compared with the standard grooming pressures . While SSecond, the visual component of receiving grooming  might have led to differential responses in the amygdala to the two forms of tactile stimuli. To control for this factor, we compared responses to grooming with and without blindfolding the animal. As shown in the example neuron in Third, we explored the possibility that reward contingencies used in the original experiments might have contributed to the observed results. In the initial design, reward was delivered after each sequence of 11 airflow stimuli. During grooming blocks, however, the animal received reward only after the block was completed. This led to substantially different intervals of time between rewards that could have altered the animal’s reward expectations and potentially altered responsiveness in the amygdala. Therefore, we inverted the reward scheme by providing reward after each set of grooming stimuli and provided reward only at the end of airflow blocks. This change had no effect on the observed neural responses in the amygdala . OverallFourth, we varied the predictability of stimuli, either delivering them randomly or in a particular sequence. In the standard protocol, airflow stimuli were delivered to 10 different areas of the face in an unpredictable random sequence while grooming sweeps were delivered to two locations, 10 consecutive times at each location. This grooming protocol, therefore, was predictable, perhaps increasing the likelihood of habituation and potentially reducing error prediction. For these control experiments, the pattern of delivery was reversed: airflow stimuli were delivered to the same two locations in groups of 10 sequential stimuli (as was done for standard grooming sweeps), whereas grooming sweeps were delivered to 10 different locations in a random sequence (as done for standard airflow stimuli). The time between repeated airflow stimuli was precisely 3 s, enhancing their predictability, whereas the timing between grooming stimuli was made variable, augmenting their unpredictability. These alterations in the sequencing and the predictability of stimuli did not change the responsiveness of amygdala neurons to airflow or to grooming  led to suppressed neural responses. For these experiments, the groomer was present in the recording booth during blocks of trials involving airflow stimuli. We did not find a difference in the responsiveness of amygdala neurons to airflow, whether the groomer was present or absent during airflow blocks  across airflow and grooming blocks. We used this approach, rather than standard statistical inference testing , because of the high probability of false positives when using large sample sizes,51 as we had many 1-s samples distributed over sessions often lasting an hour or longer. Furthermore, to help ensure that detected changes were not due, for example, to progressive changes in baseline over the course of an experiment, we also calculated the effect sizes across blocks of the same condition . For a neuron to be considered as showing context-related changes in baseline firing rate, the grooming-to-airflow effect size needed to exceed the standard minimum of 0.252 and be 1.5 times greater than the largest effect size of the within condition measures . Under these criteria, 60 neurons were identified as showing clear context-related baseline activity. Of these 60, 40 had baseline firing rates greater during grooming than during airflow , whereasbaseline activities of the neurons when the groomer was present and absent during airflow stimuli. When the groomer was present, baseline activity showed small but significant changes compared with airflow blocks without the groomer. Cells that showed increased baseline firing rates during grooming increased their baseline firing rate when the groomer was present during the airflow blocks  could accurately decode context from the baseline firing rates of amygdala neurons. We first determined the performance of the SVM for each of the 237 neurons using 10-fold cross-validation on 1-s bins of baseline firing rates . We founZ scores) between grooming and airflow blocks. The correlation between these variables was strong for cases where the difference in baseline firing rates was negative  and where the difference was positive . Furthermore, there was considerable overlap in neurons identified as exhibiting context-related baseline activity through SVM and those identified using the effect size criteria described above . Exceptions to this pattern pertained to a few initial sessions when monkeys may not have been adjusted to the experimental situation  remained unresponsive during grooming. Therefore, response modulation associated with prediction errors seems unlikely to account for the blunted responses during grooming.The mechanisms that account for the cessation of responses to grooming are unknown. Given that the fixed alternations of blocks and the sequencing of grooming stimuli were predictable, the suppression of responses might be attributed to the absence of a prediction error.71 Indeed, the activity of oxytocinergic neurons increase during prosocial behaviors, including social touch.73 In the amygdala, oxytocin primarily increases the excitability of inhibitory interneurons75 that could lead to suppression of principal cell activity during prosocial situations such as grooming, as observed in the present investigation.A potent neuromodulator, like oxytocin, may be responsible for changing the neuronal responses between non-social and social touch.Overall, grooming was associated with two important features in the activity of the amygdala. Neurons did not respond to individual touch stimuli through phasic departures from their baseline rate. Concurrently, in many neurons, baseline activity reflected, through small but significant changes, the context in which the stimuli occurred. Although context in the present experiments likely had multiple components, the presence of the groomer alone was sufficient to elicit changes in baseline activity, regardless of the type of tactile stimulation received. This implies that baseline activity in the amygdala may be linked to the social context.76 Indeed, in different cognitive contexts, neurons in various brain areas respond differentially to the same visual stimuli.79 Recently Jovanovic and colleagues80 showed that the baseline firing rates of prefrontal neurons in marmosets appear to signal social context. Our observation of persistent changes in baseline activity linked to social context is consistent with those findings. Furthermore, it reinforces previously demonstrated associations between long-lasting motivational states and modulation of baseline firing rates.82 Anxiety, for example, is maintained over several seconds through the elevated baseline firing rate of neurons in the amygdala.83 Likewise, memory acquired through associative learning can persist for minutes through changes in baseline firing both in the amygdala and the anterior cingulate cortex.84 Similarly, baseline activities of neurons in the basal ganglia and the cortex retain information about the outcome from multiple preceding trials to guide future behavioral choices.85 In the insula, baseline activity tracks the satiety of animals.82 Furthermore, baseline activity in multiple brain areas appears to encode the engagement of the animal with external stimuli.86Classic field studies in primatology have demonstrated that social context can affect the meaning of sensory stimuli.87 but also on inputs from larger networks that govern global brain states.89 Projections from the brainstem, hypothalamus, or from the nucleus basalis of Meynert34 that release neuromodulators into the amygdala92 may be candidates for cellular processes that govern baseline activity.The cellular mechanisms that give rise to these persistent changes in baseline activity in the amygdala are unknown. Baseline firing rates depend on the level of activity in the local network within which neurons are embedded35 the amygdala has nuanced control overvigilance,93 emotion,94 and social behavior.95 Although our subjects were seated in a primate chair and were groomed by humans, their physiological responses resembled that of macaques groomed by conspecifics in natural settings. They showed vagal tone, slowed heart rate, and muscular relaxation.24 In natural settings, the recipient of grooming typically relinquishes attentive scanning of the environment to the groomer.23 In contrast, during vigilant scanning of the environment, the amygdala seems to prepare the organism to detect and respond to salient, behaviorally meaningful stimuli.93By virtue of its role as the major hub in the brain where multiple networks intersect,96 In the amygdala, suppression of tactile sensitivity may reflect a switch from sensing individual stimuli to “feeling” an internal state. Future studies on the mechanism of sensory suppression or gating hold promise for explaining the phenomenon reported here.The lack of vigilance and the presence of vagal tone might partially account for the cessation of neuronal responses to individual tactile stimuli during grooming. Under these conditions, naturalistic grooming touches might be processed by the amygdala not as individual tactile stimuli but as a continuous stimulus that elicits a prolonged internal state. Another possibility is that while grooming-related touches were suppressed, unpredicted touches to other body regions might not be. Such behaviorally dependent gating of cutaneous input has been observed in cuneate nucleus, a site containing second-order somatosensory neurons in the lemniscal pathway.Although we partly controlled for potential effects of predictability, additional experiments in which stimuli other than the type used within a block are unexpectedly applied  would provide insight into the duration and nature of suppression of phasic responses. Relatedly, new experiments are needed to explore the role of oxytocin and other neuromodulators that may be at play in gating neural responses to external stimuli.Detailed methods are provided in the online version of this paper and include the following:kgothard@email.arizona.edu).Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Katalin M. Gothard , were prepared for neurophysiological recordings from the amygdala and somatosensory cortex. The stereotaxic coordinates of the right somatosensory cortex and right amygdala in each animal were determined  based on 3T structural magnetic resonance imaging (MRI) scans (isotropic voxel size = 0.5 mm)  and S5. Single-unit spiking activity was recorded using linear electrode arrays  with 16 (16 sessions) or 32 (32 sessions) equidistant contacts at 400 μm (16 contacts) or 200 μm (32 contacts) separation along a 260 μm diameter shaft. Data were collected using Plexon OmniPlex data acquisition hardware and software (RRID:SCR_014803). Electrode arrays were acutely lowered into the right somatosensory cortex and amygdala for each recording session using a Thomas Recording Motorized Electrode Manipulator . Impedance for each contact ranged from 0.2 to 1.2 MΩ. The anatomical location of each electrode was calculated by aligning a scaled image of the chamber to a series of coronal MR images and fiducial markers . During recordings, slip-fitting grids with 1 mm distance between cannula guide holes were placed in the chamber, allowing sampling of medio-lateral and anterior-posterior locations in the amygdala and somatosensory cortex. A twenty-three-gauge cannula was inserted through the guide holes and advanced 4–6 mm below the dura into the cortex. V-probes were then driven through the cannula and to the amygdala or somatosensory cortex at a rate of 70–100 μm/s, slowing to 5–30 μm/s after the tip of the V-probe crossed into the estimated location of the central nucleus of the amygdala or primary somatosensory cortex. Data were recorded in 48 sessions: monkey E = 9 , A = 13 , C = 13 , S = 7  and 6 (2 probes in right somatosensory cortex). See In three monkeys , heart rate was recorded using self-adhesive H59P electrocardiogram (EKG) electrodes  attached to two shaved skin patches on the animal’s back and recorded at 1 kHz. R waves, corresponding to ventricular contraction, were manually discriminated using the Plexon offline sorter.31 The airflow system delivered gentle, non-aversive airflow stimuli via computer-controlled solenoid valves through low pressure vinyl tubing that was fed through Loc-line hoses (Lockwood Products). The Loc-line nozzles were placed ~2 cm from the monkeys’ fur, aimed at ten locations on the face and head, avoiding the eyes, ears, and nose. Nozzles were placed to the left and right, adjacent to the lower muzzle, upper muzzle, brow, lateral head, and posterior head. An additional nozzle was placed behind the monkey to act as a sham control for alerting and auditory responses. The pressure detected 2 cm away from the nozzle was about 10 Pa . Delivery of airflow stimuli was controlled using custom-written code in Presentation Software . The airflow stimuli were delivered for 1s  followed by a 3 s inter-stimulus interval. Airflow stimuli were pseudo-randomly delivered to each of the 11 locations (including sham) as shown in Monkeys were seated in a primate chair and placed in a recording booth featuring a custom-made airflow delivery apparatus (Crist Instruments). The apparatus consists of a solenoid manifold and an airflow regulator connected to lock line hoses brought to the vicinity of the face .31 The aFor grooming blocks, the monkey’s trainer entered the recording booth, sat in front of the animal, and delivered gentle, grooming-like sweeps to the monkey’s face. Grooming sweeps lasted 1–2 s, followed by a 2–4 s inter-stimulus interval. Typically, the monkey received 10 grooming sweeps to the left upper muzzle, followed by 10 sweeps to the left brow. . The main reason for not applying the grooming stimuli to all face regions was the difficulty (and excessive time) in removing and re-positioning the air nozzles around the monkey’s face to give access to the experimenter’s hand for grooming. Each set of sweeps was repeated 5 times in one block. The timing and the contact pressure of the grooming sweeps were recorded using a custom-built pressure-transducer placed on the pad of the index finger inside a vinyl glove. The contact pressure of the grooming sweeps gradually increased and then decreased see , with a In a typical experimental session, three airflow blocks were interspersed with two grooming blocks. Typically, the firs block was an airflow block. The pattern was varied in about 1/3 of sessions . The durations of airflow and grooming blocks were also varied in some sessions. In a subset of sessions, control blocks were appended to the end of a standard set of blocks. To evaluate the effects of contact pressure on neural responses, we decreased or increased the airflow pressure to half and double the standard pressure. Similarly, we decreased or increased the pressure of the grooming sweeps to approximately half or double the usual pressure. Pressure controls were performed in three sessions of monkey A. To control for visual inputs from the looming hand of the groomer, we blindfolded the monkey during a set of airflow-grooming-airflow blocks . To control for the effect of differing reward contingencies between airflow and grooming, the reward schedule was reversed: instead of receiving reward between each set of airflow stimuli, the monkey received reward at the end of the entire block. Likewise, instead of receiving reward at the end of the grooming block, the monkey received rewards between each set of 10 grooming sweeps (monkey C: 2 sessions). An additional control was designed where airflow stimuli were delivered in the same pattern as standard grooming stimuli , and the grooming stimuli were delivered pseudo-randomly to 8 locations, repeated 10 times .All monkeys were trained for several weeks prior to electrophysiological recordings to acclimate them to the airflow puffers, grooming, and EKG electrodes.We recorded 615 neurons from the amygdala  and 375 neurons from the somatosensory cortex . A neuron was included in the analysis if it met the following criteria.minimum firing rate: the average firing rate across the experiment was at least 1 Hzcriterion for responsivity to tactile stimuli: stable for at least 10 trials of each airflow and grooming stimulus locations.Coloring for Colorblindness (https://davidmathlogic.com/colorblind).Spike times and waveforms were imported into MATLAB for analysis using scripts from the Plexon-MATLAB Offline Software Development Kit (Plexon). All analyses were conducted using custom scripts in MATLAB R2021b (Mathworks). Colors were tested for color-blind friendliness using online algorithms at t test. A neuron was classified as having a stimulus induced response if, in at least one stimulus location, the stimulus-baseline comparison was significant at p < 0.05 and the mean stimulus rate was at least 1 Hz different from the mean baseline rate.Stimulus induced responses were identified by comparing pre-stimulus and post-stimulus firing rates. The pre-stimulus window was defined as 1000 ms–250 ms before stimulus onset; the post-stimulus window was defined as 200 ms after stimulus onset to the end of the stimulus. The average firing rate of each of these windows was compared using a paired To compare responses between grooming and airflow stimuli, we considered airflow responses only at locations that were also grooming locations. Although we delivered airflow stimuli to 10 locations, and required at least 10 stimulations of each location, we included in the analysis responses only to the airflow locations that were also groomed e.g., the left upper muzzle and left brow.We compared responses during control and standard experimental conditions using only neurons that were active in both conditions. Proportions of cells that responded were compared using the chi-squared test of proportions.The criterion for including neurons in baseline firing rate analysis was stable firing for 4 blocks, . Concatenated segments of baseline firing rates for two grooming and two airflow blocks were generated by removing stimulus windows (with a 300-ms buffer before and after), inter-block intervals, and reward windows. The resulting baseline firing rates were binned in 1 s bins and converted to Z-scores.In the analysis of context-related modulation, we included 237 neurons from the amygdala that were stable for 2 airflow and 2 grooming blocks . We included neurons with at least 60 baseline bins (1 s bins) in each of the four blocks.47:52 and the grooming-to-airflow effect size was at least 1.5 times greater than the largest effect size of either the grooming-to-grooming or airflow-to-airflow block comparisons . We used a 10-fold cross-validation on balanced counts of airflow and grooming bins for each cell. For each neuron we also generated a null distribution by randomly assigning bins to either grooming or airflow blocks, repeated 10,000 times, and compared the upper bound of the resulting 95% confidence interval to the performance when using correctly as -signed bins .To identify the minimum population size required for accurate decoding of context, we determined the SVM performance using sets of 1–237 neurons. Balanced counts of 60 bins per block were used for all cells. For each set size, we generated 10,000 sets of randomly selected neurons from our recorded population of 237 (with replacement) and found the mean performance of the classifier and 95% confidence interval of the bootstrapped distribution.  We used the lower bound of the 95% confidence interval to determine the performance of the classifier for that set size.We applied principal component analysis (PCA) to visualize the separation of baseline activity in airflow and grooming bins . The sept test across sessions.Instantaneous heart rate was calculated as the inverse of the duration of each inter-beat interval (IBIs). Noise and movement artifacts were removed, as well as windows with biologically implausible IBIs  or greater than 240 BPM). Instantaneous heart rates were interpolated to 1 ms time-scales using a modified Akima cubic Hermite interpolation. Mean heart rates between conditions were compared using a paired RSA(t) = (RSA strength (t) − μ)/μ.Heart rate variability was calculated from noise-free heartbeat times in sliding windows of 60 s with a 3 s step, using a multi-taper power spectral density estimate with 7 Slepian tapers for ±0.07 Hz smoothing. For each spectrum, we identified peaks between 0.25 and 0.5 Hz, corresponding to respiratory rates between 15 and 30 breaths per minute. RSA strength in that time window was defined as the mean power at the peak ± half-width. The RSA strength at each time was normalized to the median strength across all time steps: We identified episodes of high heart rate durin grooming using the following approach. We first determined the mean (and SD) heart rate during prolonged periods of stable heart rate  within the grooming blocks. All grooming periods within a session were then scanned for epochs for which heart rate was >2 SD above the stable-period mean and with a duration of at least 10 s. This process identified a total of 31 high heart rate episodes in the three monkeys for whom EKG was recorded. Peri-stimulus time histograms of neural activity were generated for grooming sweeps during these epochs of high heart rate. We then applied the same criteria as described above “” to iden1


Age-related hearing loss (ARHL) is one of the main illnesses afflicting the aged population and has a significant negative impact on society, economy, and health. However, there is presently no appropriate therapeutic treatment of ARHL due to the absence of comprehensive trials.The goal of this review is to systematically evaluate and analyze recent statistics on the pathologic classifications, risk factors, treatment strategies, and drug candidates of ARHL, including that from traditional Chinese medicine (TCM), to provide potential new approaches for preventing and treating ARHL.Literature related to ARHL was conducted in databases such as PubMed, WOS, China National Knowledge Infrastructure (CNKI), and Wanfang from the establishment of the database to Jan, 2023. The pathology, causal factor, pathophysiological mechanism, treatment strategy, and the drug candidate of ARHL were extracted and pooled for synthesis.Polygonum multiflorum Thunb., Panax ginseng C.A. Mey, and Pueraria lobata (Willd.) Ohwi. Their active compounds, 2,3,4',5-Tetrahydroxystilbene-2-O-D-glucoside, ginsenoside Rb1, and puerarin, may act as the molecular substance for their anti-ARHL efficacy, and show anti-oxidative, neuroprotective, anti-inflammatory, anti-apoptotic, or mitochondrial protective effects.Many hypotheses about the etiology of ARHL are based on genetic and environmental elements. Most of the current research on the pathology of ARHL focuses on oxidative damage, mitochondrial dysfunction, inflammation, cochlear blood flow, ion homeostasis, etc. In TCM, herbs belonging to the kidney, lung, and liver meridians exhibit good hearing protection. Seven herbs belonging to the kidney meridian, 9 belonging to the lung meridian, and 4 belonging to the liver meridian were ultimately retrieved in this review, such as + channel openers, Ca2+ channel blockers, JNK inhibitors, and nerve growth factors/neurotrophic factors all contribute to hearing protection, and herbs are an important source of potential anti-ARHL drugs.Anti-oxidants, modulators of mitochondrial function, anti-inflammation agents, vasodilators, K Human ear can detect sound waves from 20 to 20,000 Hz, with frequencies between 1,000 and 3,000 Hz are the most sensitive. There sound waves enter the inner ear by two different methods: air conduction (AC) and bone conduction (BC). BC allows sound waves to pass directly through the skull to excite the periosteum, and excite the Corti to produce auditory perception, only plays a role in auditory examinations. Contrarily, AC predominates in most cases  [Age-related hearing loss (ARHL), also known as presbycusis, is a condition in which hearing loss develops gradually over time in the majority of older people. It is the third most common disease in the United States after heart disease and arthritis among diseases that primarily affect older adults . ARHL isThe pathophysiological causes and therapy options for ARHL are still poorly understood. As a result, there are no medications on the market right now that can effectively treat ARHL. However, there are many herbal medicines with great potential for treating ARHL. Traditional Chinese medicine (TCM) has a lengthy history of clinical application and a very rich body of knowledge regarding ARHL. In this review, we searched for literature in databases such as PubMed, WOS, China National Knowledge Infrastructure (CNKI), and Wanfang from the establishment of the database to Jan, 2023. The pathology, causal factors, pathophysiological mechanisms, treatment strategies, and the drug candidates of ARHL were extracted and pooled for synthesis. We summarize the types, causes, and pathophysiological mechanisms of ARHL, as well as therapy options for ARHL using both herbal remedies and contemporary medications, and their associated pharmacological consequences. This review provides a unique perspective on how herbal remedies and contemporary medications affect the mechanisms of ARHL, particularly in the treatment of ARHL with herbal remedies. We hope this will help develop drugs with potential therapeutic effects on ARHL.ARHL mostly involves lesions of the inner ear, auditory nerve, and central nervous system, and is a type of sensorineural hearing loss. Based on the pathological circumstances of the inner ear of the human temporal bone after death and its audiogram study, ARHL can be classified into sensory presbycusis, striatal presbycusis or metabolic presbycusis, neurologic presbycusis, and cochlear conduction deafness . The firIn audiograms, sensory presbycusis is defined by an increase in the high-frequency threshold, and in temporal bone dissection, by the degeneration of hair cells (HCs) near the basal turn of the cochlea. HCs include outer hair cells (OHCs) and inner hair cells (IHCs) Fig. d. SensorStriatal presbycusis, also known as metabolic presbycusis, manifests as atrophy of the stria vascularis (SV) in the temporal bone, flattening of the hearing curve on audiograms, or a minor increase in hearing threshold at high frequencies. SV cells are located on the outer wall of the cochlea duct Fig. c and areNeural presbycusis is characterized by degeneration of the auditory nerve and loss of cochlear neurons throughout the cochlea. The degeneration of spiral ganglion neurons (SGNs) may be caused by the accumulation of noise-induced loss of cochlear-nerve/hair-cell synapses , 15. Thea auditory nerve synapses, and may therefore play an important role in the development of ARHL [Unlike other sensory systems, which generally have only one or two centers, the auditory system has four centers: cochlear nucleus, superior olive nucleus, lateral lemniscus, and inferior colliculus Fig. f. The co of ARHL .Hearing loss can begin in adolescence, but most hearing loss due to biological aging begins much later, always at age 60. Numerous studies have demonstrated that as animals get older, their ABR threshold rises . BiologiBecause congenital deafness and early-onset deafness are mostly related to genetic factors , ARHL isThe granular head-like 2 gene (GRHL2) is located on chromosome 8, and the protein it encodes is a transcription factor that is associated with Deafness, Autosomal Dominant 28 (DFNA28), which is associated with ARHL in Europeans , but notThe strongest candidate for the ARHL gene is GRM7, a gene that encodes the glutamate metabolic receptor type 7. Glutamate is an excitatory neurotransmitter, impairment of glutamate homeostasis has important neuropathological consequences and is associated with a variety of neurological or neurodegenerative diseases . The preThe above suggests that the neural-related genes responsible for ARHL are mostly associated with the secretion of the excitatory neurotransmitter glutamate. Excessive secretion of glutamate can cause severe damage to neurons and HCs, leading to ARHL.N-acetyltransferase 2 (NAT2) is involved in the metabolism and detoxification of reactive oxygen species (ROS). The DNA of 68 patients with ARHL and 98 healthy controls was studied to prove that the polymorphism of NAT2*6A was significantly associated with ARHL in the population . GlutathOxidative stress is an important trigger for biological aging, and its impact on ARHL is also significant. Therefore, interfering with the oxidative stress-related genes that cause ARHL is also a treatment for ARHL.Mitochondrial DNA (mtDNA) 4977-bp deletions are often found in ARHL patients. In 17 ARHL patients and 17 normal subjects, 14 patients and 8 normal subjects showed 4,799-bp deletion respectively . Five ARThe above studies suggest that interference with mtDNA mutations in the auditory system is also a potential treatment for ARHL.In recent years, patients with ARHL have tended to be younger; one reason for this is prolonged exposure to noise. The degeneration of HCs of basal turn of the cochlea, especially the massive loss of OHCs, may be triggered by noise exposure . In old Lifestyle may affect auditory performance and progression of ARHL at any age. Smokers or passive smokers are also at high risk of developing ARHL, with passive smokers having a higher risk, and moderate alcohol consumption can reduce the risk of ARHL . A surveTherefore, people can prevent the occurrence of ARHL by maintaining good lifestyle habits such as limiting the intake of high-calorie foods, quitting smoking, moderate alcohol consumption, moderate exercise, and maintaining good sleep.+-K+-ATPase on the cell membrane, resulting in damage to HCs. Early changes caused by aminoglycosides are reversible, but beyond a certain point they become irreversible damage, with a 63% chance of hearing loss in people using aminoglycosides [Another reason why ARHL patients tend to be younger is the use of ototoxic drugs. Exposure to ototoxic drugs, such as aminoglycoside antibiotics , non-steroidal anti-inflammatory drugs, loop diuretics, antineoplastic drugs , or inhalation of harmful gases , all can cause ARHL. Cisplatin is an anticancer drug that has shown clinical efficacy against a variety of cancers. Tinnitus and high-frequency hearing loss are side effects of cisplatin use , 78. Theycosides , 80.Noise exposure and the use of ototoxic drugs can independently contribute to hearing loss in individuals of any age, but they are also important external factors that exacerbate the progression of ARHL. There are many interesting similarities between age-related, noise induced, and drug-induced hearing loss, such as the potential involvement of ROS and apoptosis and necrotic cell death . TherefoMany patients had a history of colds before the onset of ARHL, and the serological examination of the virus also demonstrated that many of the viruses were associated with hearing loss, such as Ménière's disease, and vestibular neuritis/viral labyrinthitis . The innWomen typically have better high-frequency hearing sensitivity, while males typically have better hearing at low frequencies than women , and men2O2 causes mouse auditory HCs to prematurely exhibit a senescence-like phenotype [It is widely believed that oxidative damage is an important cause of ARHL. In energy metabolism, cells are able to continuously reduce oxygen through the respiratory chain to superoxide and finally to ROS. NADPH oxidase (NOX) is an important source of ROS in the cochlea, and NOX activity increases the expression of genes involved in the excitatory pathway, damages the cochlea, and ultimately causes ARHL . Howeverhenotype . And michenotype . As a reAnti-oxidants, including vitamin C, vitamin E, GSH, coenzyme Q (CoQ), carotenoids, and melatonin are frequently utilized to combat oxidative damage , 97. Mel+)-dependent histone deacetylase with seven members (SIRT1-7), is involved in many crucial biological processes, including apoptosis, endocrine signaling, glucose homeostasis, aging, and longevity [Mitochondrial dysfunction in cochlear cells can be caused by inhereditary mtDNA mutations, accumulation of acquired mtDNA mutations with age, mitochondrial overdrive and calcium dysregulatio, or accumulation of ototoxic drugs in hair cell mitochondria . The Sirongevity . It is aongevity .+ levels and activating SIRT1 in the cochlea [Resveratrol, a natural polyphenolic compound that could activate SIRT1, is found in a variety of plants, such as grapes, berries, mulberries and peanuts . Resvera cochlea .A variety of factors can cause cochlear inflammation, such as biological aging, noise, otitis media, use of ototoxic drugs, radiation damage, etc. After the cochlea is damaged, TNF-α is expressed in the cochlea, which in turn stimulates other cytokines such as IL-1β and IL-6 to concentrate in the cochlea, thereby increasing the production of free radicals in the auditory system and causing hearing loss , 119. Th+ T cells lacking regulatory T cells and IL-1 receptor type 2-expression T cells into a mouse model of ARHL and found that it prevented ARHL development and SGN degeneration [Currently, the most widely used medication for sudden deafness is corticosteroid, an anti-inflammatory drug. These drugs are usually taken orally or injected into the body , but they can also be directly injected into the middle ear through the tympanic membrane  . The effneration , which mThe labyrinthine arteries, which are virtually the only blood supply arteries to the inner ear, provide the majority of the blood flow to the inner ear. The inner ear's ability to function is significantly impacted by its lesions. According to some animal studies, EP disappears after 6 s of ischemia in the inner ear. Even when the blood supply is restored after 30 min of ischemia, the loss of EP remains irreversible. Therefore, cochlear microcirculation abnormalities are one of the causes of NIHL , ARHL 1, and oto2+) and antioxidant free radical scavenger can better improve hearing function [2+. They also reduce the concentration of intracellular Ca2+. Alternatively, histamine injections can be used as an adjuvant to increase the permeability of the inner ear to dexamethasone. Intratympanic injection of 1% histamine and steroids may be a safe and effective treatment for hearing loss [Several vasodilators have been shown to have the potential to treat different types of hearing loss by improving microcirculation in the blood-labyrinth barrier, maintaining EP, maintaining cochlear endolymphatic production, and reducing the build-up of toxic and inflammatory substances in the cochlea. The combination of cochlear vasodilator  is expressed in SV, which can regulate the concentration of K+ in the scala media and play a key role in the production of EP. Studies have found that the expression of NKCC1 has declined with the development of ARHL [+-K+-ATPase circulates K+ from the perilymph to the endolymph to regulate the resting potential in the scala media, and studies have found that the decrease of EP amplitude was significantly related to the stria vascularis and spiral ligament fibrocytes (type II), which are rich in Na+-K+-ATPase [The cochlea is spiral-shaped and consists of scala vestibuli, scala media and scala tympani Fig. c, the sc of ARHL . Na+-K+-+-ATPase . Cav1.3 +-ATPase . Hearing+-ATPase . As a re+ channel openers, such as zinc pyrithione, retigabine, and Maxipost, can restore K+ channel function and prevent hearing loss and tinnitus caused by aminoglycosides and salicylates [2+ channel blockers have also demonstrated protective effects against ARHL. For instance, T-type Ca2+ channel blockers were able to significantly preserve SGN [Kicylates , 137. Nuerve SGN , 139 whierve SGN .Damage to the inner ear causes the death of HCs, with OHCs usually being lost first, followed by IHCs and finally the supporting cells of the organ of Corti. In general, apoptosis is controlled by pro-apoptotic factors (caspases family and cytochrome c (Cyt-c)) and anti-apoptotic factors (Bcl-2 family) , 142. He± mice had worse hearing progression after noise stimulation and lower plasma levels of IGF-1 [As previously mentioned, cochlear neuron loss plays a significant role in ARHL. Nerve growth factor (NGF) levels in the blood were significantly lower in patients with sensorineural hearing loss . Studiesof IGF-1 .Several growth factors prevent degeneration of cochlear neurons, such as NGF , neurotrA hearing aid is a device that amplifies sound to improve the perception of sound by a hearing loss patient. Hearing aids do not restore a patient’s damaged hearing, but they can use the patient’s residual hearing to enhance the patient’s speech recognition ability and improve the patient’s quality of life and work. It is currently the most widely used treatment for hearing impaired patients. Following clinical hearing aid therapy, the ARHL group showed a reversal of cross-modal reorganization of visual to auditory cortex, which was accompanied by alterations in speech perception and cognitive function .A cochlear implant is an electronic device that reconstructs or acquires hearing for patients with severe, profound or total hearing loss. It mimics the function of the cochlea and converts acoustic signals into electrical signals, replaceing the function of damaged HCs and directly stimulating the SGN, which then transmits the electrical signals to the brain to produce hearing. Cochlear implants are an option to help if a person has significant hearing loss and hearing aids are insufficient to enhance sound in that situation. Through the cognitive function test of the elderly one year after the cochlear implant operation, it was found that the cognitive benefits of the elderly with cognitive impairment before the cochlear implant were even greater than those of the subjects with normal cognition .However, cochlear implants require surgery, which many individuals decide against because of concerns about getting older and the state of the economy. And cochlear implant surgery can induce cellular inflammatory reaction and foreign body reaction, leading to cochlear injury, which may further aggravate hearing loss . MoreoveHyperbaric oxygen therapy: A controlled trial of 60 ears with hearing impairment and tinnitus that received hyperbaric oxygen therapy and 60 ears that received normoxic therapy found that patients treated with hyperbaric oxygen therapy had significantly better hearing and tinnitus recovery . Recent Most patients with ARHL or sensorineural hearing loss have no specific cause of hearing loss, and systemic or intratympanic steroid therapy has become a common treatment for patients with sensorineural hearing loss . HoweverAccording to TCM theory, the kidney opens into the ear. Compared with the general population, patients with chronic renal failure are more likely to also experience sensorineural hearing loss. The study found that the incidence rate is 77% . BecausePolygonum multiflorum Thunb., its flavor is bitter, sweet, and astringent, and its nature is slightly warm, belonging to the liver and kidney meridians. It is frequently used as a tonic or anti-aging agent in several regions of Asia and is frequently utilized in clinics to treat a wide range of chronic conditions [Polygonum multiflorum Thunb. It was found that THSG has a similar free radical scavenging capacity to ascorbic acid, and can prevent H2O2-induced autophagy in UB/OC-2 cells and inhibit H2O2-induced apoptosis through the mitochondrial pathway. The mRNA expression of HO-1 and NQO1 increased as a result of Nrf2 translocation to the nucleus, suggesting that THSG can enhance antioxidant defense against oxidative stress and play a role in hearing preservation [Polygonum multiflorum Thunb. should not be consumed in large doses over an extended period of time due to the possibility of liver damage.nditions . 2,3,4’,ervation . Additioervation . HoweverDrynaria fortunei (Kunze) J.Sm., its flavor is bitter and warm in nature, and belongs to the liver and kidney meridians. It has been used to treat fractures with good results. It is frequently combined with Rehmannia glutinosa Libosch. and Cornus officinalis Sieb. et Zucc when treating tinnitus and hearing loss due to by kidney failure. Studies have shown that Drynaria fortunei (Kunze) J.Sm. can protect against the ototoxicity of aminoglycosides and streptomycin in guinea pig cochlear HCs, hence defending hearing [Drynaria fortunei (Kunze) J.Sm. may be its active ingredient. It can protect the ototoxicity of animals caused by gentamicin, and the damaged both IHCs and OHCs recover well without hindering the efficacy of gentamicin [ hearing , 169. Thntamicin .Cornus officinalis Sieb.et Zucc., it has a sour and astringent flavor, is slightly warm in nature, and belongs to the liver and kidney meridians. It is one of the ingredients in the Erlong Zuoci which is a traditional deafness prescription  Juzep., Poria cocos (Schw.) Wolf, Paeonia suffruticosa Andr., Dioscorea opposita Thunb., Bupleurum chinense DC.), this prescription has been shown to elimination of DNA damage in hydrogen peroxide-induced auditory HCs, blocks up-regulation of cellular senescence proteins p21 and p-p53, increases p-ERK  expression, reduces p-STAT3 (STAT3 activation is closely related to cancer) expression [Cornus officinalis Sieb. et Zucc., can inhibit lipid peroxidation in a dose-dependent manner and activate the antioxidant enzymes CAT and GPx to prevent damage to auditory HCs caused by hydrogen peroxide [pression , and propression . Ursolicperoxide .Rehmannia glutinosa Libosch., its flavor is sweet, slightly warm in nature, and belongs to the meridians of the liver and kidneys. It nourishes the liver and kidneys, and is used to treat tinnitus and hearing loss due to liver and kidney deficiency. It is often used in conjunction with Cornus officinalis Sieb.et Zucc. and Dioscorea opposita Thunb., it is the monarchical medicine of the six-flavor Rehmannia Decoction, a common tonic. And it has been shown that six-flavor Rehmannia Decoction could effectively reduce the ototoxic effect of gentamicin on the inner ear of guinea pigs [Rehmannia glutinosa Libosch. can protect auditory cells from the ototoxicity of cisplatin in a dose-dependent manner, and its pharmacological effects may be related to the activation of intracellular anti-oxidant enzymes and inhibition of lipid peroxidation [nea pigs . Ethanolxidation , 176.Sesamum indicum L., has a sweet flavor, is flat in nature, and belongs to the liver, kidney, and large intestine meridians. This is a great food to supplement the body’s nutrition. Rich in Sesamum indicum L. oil and sesamin, Sesamum indicum L. oil decreased the hearing threshold changes caused by clicks and 8,16-kHz tone bursts in NIHL mice and it improved hearing impairment. Additionally, research on the hearing-related gene Tecta revealed that sesamin plays a crucial protective role in auditory function by shielding auditory HCs from damage and reversing it [rsing it .Tripterygium wilfordii Hook. f., which has a bitter and pungent flavor, is cold in nature, highly poisonous, and belongs to the liver and kidney meridians. It is mainly used to treat rheumatoid arthritis. One of the key components of Tripterygium wilfordii Hook. f., Celastrol, is a pentacyclic triterpenoid compound that inhibits ototoxicity by activating heat shock protein (HSP) 32/heme oxygenase-1 (HO-1) and NF-E2-related factor-2  in HCs in neomycin-treated mice [Tripterygium wilfordii Hook. f., users frequently report unpleasant side effects like diarrhea, indigestion, nausea, abdominal pain, and upper respiratory infections [Tripterygium wilfordii Hook. f. is extremely risky.ted mice . Recent ted mice . Howeverfections . ConsequPoria cocos (Schw.) Wolf, its flavor is sweet and mild, is flat in nature, returns to the heart, lungs, spleen and kidney meridians. Studies have shown that the decoction of Poria cocos (Schw.) Wolf can prevent kanamycin-induced ototoxicity in guinea pigs [nea pigs .Glycine max (L.) Merr. and peels of Punica granatum L. belong to the large intestine meridian rather than the lung meridian. However, TCM theory holds that there is an exterior-interior relationship between the lung and the large intestine, and that the dysfunction of the large intestine also cause lung diseases. There is currently pertinent research showing the intimate connection between the large intestine and the lung [There are many related theories of lung and hearing loss in TCM, “lung main Qi, one’s Qi passes through the ear, so can hear sound”, and some hearing loss is triggered by a cold, and cold is also associated with the dysregulation of lung function, so it is believed that lung and hearing loss have a close relationship. In addition, the lung . TherefoPueraria lobata (Willd.) Ohwi, its flavor is sweet and pungent, cool in nature, returns to the spleen, stomach, and lung meridians, and is mostly used for the treatment of cardiovascular and cerebrovascular diseases and hearing loss [Pueraria lobata (Willd.) Ohwi, which had a good preventative impact on senile diseases in rats [Pueraria lobata (Willd.) Ohwi is puerarin, an isoflavone compound. Studies have shown that puerarin treatment can significantly improve the threshold of auditory brainstem response (ABR) in NIHL mice. It was discovered through research on the cochlear nucleus in the central auditory pathway that it reduced the expression of the protein kinase C gamma subunit (PKCγ) after noise exposure and increased the decrease of GABAB receptor 1 (GABABR1) and GABABR2; this may be one of the pharmacological mechanisms of its effect [ing loss . Rats' h in rats . The mais effect .Astragalus membranaceus (Fisch.) Bge., its flavor is sweet, slightly warm in nature, and returns to the meridians of the spleen and lungs. It is often combined with Panax ginseng C.A. Mey., Cimicifuga foetida L., and Bupleurum chinense DC., such as Buzhong Yiqi Decoction, a TCM formula for deafness and tinnitus caused by spleen deficiency. Astragalus membranaceus (Fisch.) Bge. is a natural anti-oxidant. Injections of Astragalus membranaceus (Fisch.) Bge. can promote the recovery of sudden hearing loss [Astragalus membranaceus (Fisch.) Bge. was able to significantly reduce ABR defects and SV damage caused by impulse noise, and reduce the shift of expression of Cx26 and KCNQ1 in SV [Astragalus membranaceus (Fisch.) Bge., has been found to significantly reduce ABR deficiency in impulsive noise-induced hearing loss and reduce ROS and the expression of cas-3 by intragastric administration of astragaloside IV to guinea pigs [ing loss . AstragaQ1 in SV . Astraganea pigs .Scutellaria baicalensis Georgi, its flavor is bitter, cold in nature, belongs to the meridians of the lungs, gallbladder, spleen, large intestine and small intestine. It is commonly used to remove heat and harmful substances in the body, promote blood circulation and remove blood stasis, and induce diuresis to reduce edema [Scutellaria baicalensis Georgi extract significantly reduced the threshold shift, central auditory function impairment and cochlear function defect, indicating that Scutellaria baicalensis Georgi can protect the auditory function of animals [ce edema . A study animals . Baicale animals . Baicale animals .Panax ginseng C.A. Mey., its flavor is sweet and slightly bitter, is slightly warm in nature, and belongs to the meridians of the spleen, lungs, heart and kidneys. It is a key drug for the prevention of critical diseases and has been used for thousands of years in TCM to treat diseases of Qi deficiency. Red ginseng is a steamed product of Panax ginseng C.A. Mey. With its anti-ROS properties, Korean red ginseng can prevent hearing loss induced by cisplatin and the mitochondrial toxin 3-Nitropropionic Acid (3-NP) [Panax ginseng C.A. Mey., can reduce hearing loss in rats caused by gentamicin by attenuating the production of ROS and inhibiting cell apoptosis [Panax ginseng C.A. Mey. that can treat hearing loss [ginseng may cause excitatory side effects and aggressive behavior in mice [d (3-NP) , 194. Stpoptosis . Ginsenoing loss . However in mice .Panax ginseng C.A. Mey. was found to improve tinnitus symptoms and mental health in people with chronic tinnitus [Panax ginseng C.A. Mey. could reduce noise-induced temporary threshold shift in textile workers exposed to occupational noise [Panax ginseng C.A. Mey. in the treatment of hearing loss and its active constituents.In an open-label randomized controlled trial of 61 patients, tinnitus . Co-treaal noise . The resStephania tetrandra S. Moore, its flavor is bitter, cold in nature, belongs to the meridians of the bladder and lungs. It is used to treat rheumatoid arthritis, edema in the lower extremities, and dysuria. Its main chemical isolate is tetrandrine, which significantly attenuates NIHL in CBA/CaJ mice, which by blocking Ca2+ channels, prevents and protects neurotrauma, prevents damage to OHCs and synapses, and has durable protection against noise exposure effect [e effect .Allium sativum L., which has a spicy flavor, warm in nature, returns to the spleen, stomach and lungs meridians. It is a common excipient in dishes and has the functions of killing parasites and detoxifying. Male Wistar rats treated with Allium sativum L. diet showed a substantial reduction in the gentamicin-induced rise in hearing threshold [Allium sativum L., protects SGN mitochondria from damage and reduces the release of Cyt-c, as well as significantly reducing the expression of cisplatin-activated pro-apoptotic factors, including Bax, cas-9, cas-3 and p53. It can also decrease malondialdehyde (MDA) levels while increasing SOD levels [Allium sativum L. has three active compounds: S-Allylmercaptocysteine (SAMC), Diallyl Disulfide (DD), and S-Allylcysteine (SAC), all of which are capable of lowering the ototoxicity of aminoglycosides. SAMC and DD seem to be more prevalent than SAC [hreshold . AllicinD levels . Allium than SAC .Ginkgo biloba L., with its sweet, bitter, and astringent flavor, is neutral in nature, returning to the heart and lungs meridians. Ginkgo biloba L., a popular anti-oxidant herbal remedy with anti-cancer and anti-aging properties, has been used to cure illnesses for more than 5,000 years. The active ingredient in Ginkgo biloba L. for the treatment of hearing loss is Ginkgo biloba L. extract (EGb 761), which consists of about 80 different compounds. EGb 761 was able to prevent NIHL in guinea pigs, and there have higher amplitudes of the acoustic nerve potentials in EGb 761-treated animals than in untreated animals [Ginkgo biloba L. extracts in the treatment of cells and neural stem cell proliferation [Ginkgo biloba L. extract, exerts a protective effect on cisplatin-induced ototoxicity in rats without weakening the antitumor activity of cisplatin [ animals . EGb 761 animals . It prot animals , 207, an animals –210. Addferation . It alsoferation . By inhiferation . EGb 761feration . Ginkgolisplatin , 216.Ginkgo biloba diterpene lactone supplementation were significantly greater than those receiving methylprednisolone alone, especially those with severe hearing loss [Ginkgo biloba L. extract may be effective as an adjunct to corticosteroids in the initial treatment of moderate to severe sudden sensorineural hearing loss [Ginkgo biloba L. still require large cohort studies, as investigations of Ginkgo biloba L. extracts have only been performed in animal models and in a small number of groups.By investigating 56 patients with unilateral sudden sensorineural hearing loss, it was found that the pure-tone audiometric gains of patients receiving ing loss . Ginkgo ing loss . Accordiing loss . StudiesPunica granatum L., its flavor is sour and astringent, is warm in nature, and belongs to the meridian of the large intestine. The peel of Punica granatum L. is commonly used to treat diarrhoea. The peel of Punica granatum L. extract has a protective effect on gentamicin-induced ototoxicity in Wistar albino rats and can reduce the level of cochlear ROS [lear ROS , and it lear ROS .Glycine max (L.) Merr. is a very common meal that contains a variety of proteins. β-Conglycinin (β-CG) is one of the main proteins in Glycine max (L.) Merr., which has anti-obesity and anti-atherosclerosis effects. Hearing impairment was protected in mice fed β-CG, it can increase cochlear blood flow and has anti-oxidative stress effects [Glycine max (L.) Merr. is also rich in lecithin. Studies have found that lecithin can significantly reduce the specific deletion of mtDNA in the cochlea, protect mitochondrial function, and thus play a role in hearing protection [ effects . Glycineotection .Emotion and hearing loss are closely related to one another. According to the TCM theory, the liver is associated with irritability, the liver is stored in blood and the kidney is stored in essence, and since essence and blood share the same origin, liver and kidney dysfunctions are also closely related to hearing loss. Many hearing loss patients also experience excessive anger and hyperactivity of liver yang.Salvia miltiorrhiza Bge., its flavor is bitter, slightly cold in nature, returns to the heart and liver meridians. It is commonly used to treat blood stasis syndrome. It can reduce the increase of hearing threshold, alleviate cell apoptosis, reduce the oxidative damage of cochlear ultrastructure such as SV and SGN, and has a protective effect on guinea pig ototoxicity caused by gentamicin and cisplatin [isplatin , 225. Taisplatin .Curcuma longa L., its flavor is pungent and bitter, warm in nature, returns to the liver and spleen meridians. It is commonly used to treat blood stasis syndrome and rheumatic pain. Curcumin is one of its main active ingredients, which can increase the survival rate of OHCs, reduce the expression of 4-HNE, and increase HO-1 expression, attenuates cisplatin-induced hearing loss [ing loss , and stuing loss . A synthing loss .Uncaria rhynchophylla (Miq.) Miq.ex Havil, its flavor is sweet, cool in nature, returns to the liver and pericardium meridians. It is commonly used to treat epileptic seizures. It has been studied that treatment with a hydrophilic chemotype carboxy alkyl esters of Uncaria tomentosa almost completely restored noise-exposed OHCs function and limited the extent of cell loss, inhibiting the loss of neural sensitivity to pure tone stimulation [mulation , which mErythrina variegata L., has a bitter and acrid flavor, is flat in nature, and belongs to the liver meridian. It is commonly used to treat lower body rheumatoid arthritis. Erythrivarines J-N and erythrivarines O-Z are alkaloids isolated from the peel of Erythrina variegata L., and studies have shown that erythrivarine N and erythrivarine T have neuroprotective effects on neomycin-induced hearing loss [The peel of ing loss , 232.The pathophysiological mechanisms responsible for hearing loss and the corresponding herbal remedies and contemporary medications are shown in Fig. + channel openers, Ca2+ channel blockers, JNK inhibitors, and nerve growth factor/neurotrophin all contribute to hearing protection. Healthy living habits, such as avoiding the use of ototoxic drugs, avoiding noise exposure, not smoking, consuming moderate amounts of alcohol, exercising in moderation, ensuring quality sleep, and eating more anti-oxidant foods also help for preventing ARHL. ARHL patients can also improve speech recognition in noisy environments by training [ARHL not only affects the independent living ability of elderly people, but may also lead to a number of mental illnesses in elderly patients. However, there are presently no efficient therapeutic drugs for ARHL. This review suggests that the main causes of ARHL are genetic and environmental factors. Currently, research on the pathology of ARHL mainly focuses on oxidative damage, mitochondrial dysfunction, inflammation, cochlear blood flow, ion homeostasis and other aspects. Anti-oxidants, mitochondrial function regulators, anti-inflammatory drugs, vasodilators, Ktraining . Moreovetraining . There atraining .Phellodendron chinense Schneid, Coptis chinensis Franch., Alisma orientale (Sam.) Juzep., Paeonia suffruticosa Andr., Bupleurum chinense DC., etc. On the contrary, some herbal medicines lead to the occurrence of NIHL, such as Ephedra sinica Stapf [Areca catechu L. [In traditional Chinese medicine, herbal medicines belong to the meridians of kidney, lung, and liver have good hearing protection. In this review, we ultimately found 7 herbal medicines belonging to the kidney meridian, 9 to the lungs meridian, and 4 to the liver meridian. Thus, Chinese herbal medicines are an important source of potential anti-ARHL drugs. In addition to the herbal remedies already mentioned, there are numerous other herbs for treating hearing loss and tinnitus that have been used in China for thousands of years but have not yet undergone thorough research, such as ca Stapf , Areca ctechu L. , and cintechu L. . The mectechu L. . Intervetechu L. .This review summarizes the potential therapeutic effects of herbal remedies on ARHL to date and the pharmacological mechanisms involved. It provides researchers with an inspiration: the focus of treatment for ARHL can be on herbal remedies. However, these herbal remedies still have some limitations: the active ingredients in the herbs are less stable and can be easily affected by temperature, humidity, light, and other factors; currently, there is a lack of scientific and reasonable clinical research to prove the efficacy of traditional Chinese medicine; it is difficult to fully determine the active ingredient of herbal remedies for ARHL due to its complex composition. These issues are in urgent need of further future research.


The prevalence of functional disabilities, including difficulties in performing activities of daily living (ADLs) and instrumental activities of daily living (IADLs), increased significantly in recent years and burdened the healthcare system.We analysed data from Korean Longitudinal Study of Aging (KLOSA) surveys, including participants aged 65 or older at baseline (2008), and participated in all 4-year follow-up periods in 2012, 2016, and 2020. A 4-year follow-up cohort study was applied to specify the change in functional disability and its trend over time among older adults. The generalized estimation equation (GEE) model was used to verify the uptrend of functional disability. Logistic regression analyses were applied to examine the influence of demographic and health parameters on the change in functional disability.The prevalence of ADL disability was 2.24% at baseline, increased to 3.10% after four years, 6.42% after eight years, and reached 11.12% after 12 years, five times higher than that at baseline. For IADL disability, they were 10.67%, 10.61%, 18.18%, and 25.57%, respectively. The uptrend of ADL disability in persons aged 65–74  was slower than in those aged 75 or older . IADL disability were consistent with this. The high ADL/IADL disability rate was also present among persons with poor health status, physical inactivity, depression, dementia, and multiple chronic diseases. The relative risk of ADL/IADL disability in persons with a history of functional disability was significantly higher than in those without historical disabilities.The study verified the change in functional disability and its upward trend over time by older adults’ demographic and health parameters. Functional disability was relatively flat tending to increase slowly during the early years but increased rapidly in the following years. Factors that strongly influenced the change in prevalence and the uptrend of functional disability were advanced age, living alone, being underweight or obese, poor health status, physical inactivity, depression, dementia, having multiple chronic diseases, and especially having a historical disability. Population aging in Korea has taken place rapidly in recent years. According to 2021 data from the South Korea Age structure . The rapAlong with the global population aging, the prevalence of functional disabilities, including difficulties in performing activities of daily living (ADLs) and instrumental activities of daily living (IADLs), has increased significantly in recent years and affected the quality of life . DeficieIdentifying the trends of disability was essential and has received much attention recently –6, 21–24In this paper, we performed a 4-year follow-up study to determine the prevalence of functional disability and its trend over time among older adults using a nationally available dataset. The factors affecting the change and trend of functional disability were also simultaneously examined.The Korean Longitudinal Study of Aging (KLOSA) data was an extensive dataset collected based on a representative nationwide survey every two years through individual interviews , 27. TheFor research purposes, we conducted a 4-year follow-up cohort study with a 2008 baseline and three 4-year follow-up periods in 2012, 2016, and 2020. To account for participants, we included all persons aged 65 or older (older adults) who participated in and completed questionnaires in all four KLOSA surveys. The final sample was composed of 1744 older participants. Figure KLOSA surveys considered the ADL scale from seven indicators: dressing, washing, bathing, eating, getting in/out of bed, toileting, and managing bladder/bowel , 26. The2; normal, 18.5–22.9 kg/m2; overweight, 23–25 kg/m2; and obese, > 25 kg/m2, based on the Asia-Pacific classification [Demographic and health parameters at baseline (2008) were considered in our research criteria. Demographics included gender , age in years , living arrangement , and educational status . Health parameters were body mass index , self-rfication ), cognitfication . This exfication , 31.We examined the change in the prevalence of ADL/IADL disability among older participants after every 4-year follow-up period from baseline (2008) through 2020 to verify the trend of this change. The change after 12 years was also demonstrated. Bivariate analyses were performed to identify participant characteristics and estimate the prevalence of ADL/IADL disability. Fisher’s exact test  calculatMultiple logistic regression models  were conWe included 1744 older adults, of which 1046 (approximately 60%) were female and 332 (19.04%) were oldest-old (aged 75 or older). The proportion of persons living alone was 26.55%. Those with elementary or lower education accounted for the highest percentage (approximately 68%), while college graduates or higher accounted for only 6.31%. Regarding health parameters, underweight persons accounted for a low rate (3.15%), while overweight or obese persons accounted for over 51%. Those with “bad” self-rated health or having difficulty in daily activities related to body pain accounted for significant rates (over 32%). Up to 63.47% of participants reported physical inactivity, 6.59% suffered from depression, approximately 35% experienced cognitive decline or dementia, and 68.23% had at least one chronic disease. The baseline characteristics of participants are shown in Table The prevalence of ADL disability increased rapidly over time. The overall rate was 2.24% at baseline, increased to 3.10% after four years, 6.42% in 2016, and 11.12% in 2020. The change after 12 years was 8.88%. By gender, the upward trend over time occurred in both males and females, but there was no significant difference between males and females at baseline . The prevalence of ADL disability in females increased more slowly than in males in 2012 but more rapidly in the following years. The change in prevalence of ADL disability after 12 years in males and females was 8.16% and 9.37%, respectively. By age group, the upward trend over time of ADL disability in persons aged 65–69  was slower than in those aged 70–74  and those aged 75 or older . By health parameters, the change in prevalence of ADL disability after 12 years was most significant among underweight and obese individuals , while the upward trend over time of ADL disability presented more slowly in overweight individuals . The prevalence of ADL disability in those with “good” self-rated health was smaller and increased more slowly than in those with “bad” self-rated health . Regarding cognitive function, the prevalence of ADL disability in persons with a normal level was the lowest, and the upward trend over time was also slower . In contrast, these rates in persons with dementia were substantially high and increased rapidly over time . The prevalence of ADL disability increased rapidly in persons with at least three chronic diseases . The prevalence of ADL disability and its trends are shown in Table The prevalence of IADL disability and its trends are shown in Table The time-varying trends of functional disability by gender and age groups are illustrated in Fig. The change over time of ADL/IADL disability in persons without disabilities at baseline is illustrated in Fig. The results of multiple logistic regression analyses are shown in Table The obtained results showed the differential influence of parameters at baseline on ADL/IADL disability among 4-year follow-up periods in 2012, 2016, and 2020. ADL disability in 2012 was significantly associated with all demographic and health parameters at baseline . The factors that had strong influence on the change of ADL disability in all 4-year follow-up periods  were age of 75 years or older , poor health status , physical inactivity , depression , three or more chronic diseases , and historical ADL disability . Historical ADL disability was the strongest factor among all parameters. Similar to ADL disability, IADL disability in 2012 was significantly associated with most demographic and health parameters at baseline, except for living alone, having high school education, and being overweight or obese. The factors that strongly predicted the change of IADL disability in all 4-year follow-up periods were age of 75 or older , depression , dementia , three or more chronic diseases , and historical IADL disability .Functional disability in older adults has presented many obstacles to policymakers and national healthcare systems, especially in recent years, as global population aging has taken place rapidly , 5. TherOur study found that prevalence of ADL disability increased slowly in the earlier years while IADL disability was stable. The prevalence of these disabilities then tended to increase rapidly over time, especially in persons aged 75 or older. The upward trends for both ADL and IADL disability were statistically significant. The results on disability trends were consistent with previous studies , 8, 25. The ADL and IADL scales both identified functional disability but measured different aspects, so trends for IADL disability differed from trends for ADL disability . TherefoThis study found factors strongly associated with the change of functional disability during a long follow-up period. These factors included advanced age, living alone, poor health status, physical inactivity, depression, dementia, multiple chronic diseases, and a history of disability. Especially significant 12-year changes in ADL disability were observed in persons aged 75 or older (21.68%), persons living alone 12.09%), those with poor health status (12.57%), and persons with dementia (21.88%). Similar to IADL disability, the change was 28.01% for those aged 75 or older, 19.87% for persons living alone, 19.43% for those with poor health status, and 19.38% for persons with dementia. Except for historical disability, these factors were consistent with and were reported in previous studies related to functional disability %, those , 15–17. Some interesting findings in this study were related to living arrangements and educational status of those with IADL disability changes. There was no significant difference in IADL disability either between living with relatives and living alone or among educational levels at baseline; however, both living alone and elementary or lower education groups significantly changed in IADL disability after 12 years. Although social-economic parameters including educational status in older adults have been well known as the strong factors for health, living alone and elementary or lower education groups demonstrated significant changes in IADL disability. The prevalence of older adults living alone is currently globally increasing, especially for older male adults . These fWe found that the prevalence of functional disability in the underweight group was higher and tended to increase more rapidly than in the overweight group, whereas it was lower and increased more slowly than in the obese group. This finding is different and has not been explained by previous studies from Korea that BMI had a negligible effect on ADL/IADL disability among Korean older adults , 40. A rOur findings also indicated that the overall prevalence of ADL disability was lower in males than in females. However, among those with dementia, males tended to have higher ADL and IADL problems. This has also been presented in previous studies . AlthougIn this study, historical disability was considered an essential factor affecting the progress of future functional disability. This aspect has not been studied comprehensively and systematically in the previous studies. Our study found that historical disability was the strongest factor among parameters that predicted the change in later disability. Specifically, the relative risk of ADL disability development in persons with an ADL disability at baseline was increased more than four times after four years compared with those without ADL disability at baseline. The number in those with IADL disability at baseline was 4.7 times higher than those without IADL disability at baseline. The same was true for IADL disability. This showed that early identification of historical disability was influential in reducing the development of severe disability.Our study had several limitations. First, this study did not include several parameters such as living region, income, smoking status, and alcohol consumption to minimize missing data. Second, this study only focused on older adults who participated in all surveys over a long period of time, so it omitted an important group including those who lost follow-up due to death or discontinuation of the process. However, it is difficult to further include this group in the analysis due to the lack of relevant information. In addition to the unreported deaths, a few persons, despite their good health, for personal reasons did not continue to participate. Third, to reduce complexity, this study was only concerned with the presentation of functional disability in general, not with regard to the distribution of the number of ADL and IADL items. Lastly, instead of assessing the influence of each chronic disease on functional disability, we only looked at the existing number of chronic diseases. This was convenient for the presentation of research results. A comprehensive and systematic study of the differential influence of chronic diseases on functional disability in general and each item of functional disability in particular is necessary for future studies.The study verified the change in functional disability and its uptrend over time by older adults’ demographic and health parameters. Functional disability tended to increase slowly, or flatly, during the earlier years but increased rapidly in the following years. Factors strongly influencing the change in prevalence and the upward trend of functional disability over time were advanced age, living alone, being underweight or obese, poor health status, physical inactivity, depression, dementia, multiple chronic diseases, and especially a history of functional disability.


To understand the effect of age on health‐related quality of life (HRQoL) in patients with hearing loss and determine how primary language mediates this relationship.Cross‐sectional study.General otolaryngology clinic in Los Angeles.Demographics, medical records, and HRQoL data of adult patients presenting with otology symptoms were reviewed. HRQoL was measured using the Short‐Form 6‐Dimension utility index. All patients underwent audiological testing. A path analysis was performed to generate a moderated path analysis with HRQoL as the primary outcome.p < .001). However, the direction of this association was reversed by hearing loss. Older patients exhibited significantly worse hearing (p < .001), which was negatively associated with HRQoL (p < .05). Primary language moderated the relationship between age and hearing loss. Specifically, patients who did not speak English as a primary language had significantly worse hearing (p < .001) and therefore worse HRQoL (p < .01) than patients who spoke English as a primary language with hearing loss. Increasing age was associated with bilateral hearing loss compared to unilateral hearing loss (p < .001) and subsequently lower HRQoL (p < .001). Polypharmacy (p < .01) and female gender (p < .01) were significantly associated with lower HRQoL.This study included 255 patients . Age had a positive direct association with HRQoL (Among otolaryngology patients with otology symptoms, older age and not speaking English as a primary language were associated with worse hearing and subsequently lower HRQoL. Age is one of the strongest predictors of hearing loss.While the extent and impact of aging on hearing loss may differ from person to person,This study addresses these gaps by investigating the effects of hearing loss on the association between age and HRQoL and examining the role of primary language on hearing loss and HRQoL among patients with otology symptoms. We hypothesized that (1) hearing loss will mediate the association between age and HRQoL, and (2) the negative impact of aging and hearing loss on HRQoL will be amplified in patients who do not speak English as a primary language.Data was collected from a chart review of patients aged 18 years and older at a general otolaryngology clinic in Los Angeles who underwent audiological testing and reported 1 or more otology symptoms including hearing loss, tinnitus, ear pressure, vertigo, dizziness, otalgia, ear pruritus, otorrhea, and phonophobia. Patients with otology symptoms who did not undergo audiological testing were excluded from the study. The study was approved by the Institutional Review Board at the University of Southern California.Demographic covariates collected from medical records included age (years), self‐reported gender , self‐reported ethnicity , self‐reported race , and primary language . To determine one's primary language, the physician asked for each patient's primary language at the start of the encounter and documented the response in the medical chart.Speech‐frequency pure‐tone averages (PTAs) were used to measure hearing loss severity. Audiometric testing was performed in English. The audiologist explained the test using a certified translator. The speech‐frequency PTA was calculated across 3 test frequencies: 0.5, 1, and 2 kHz. Separate PTAs were calculated for each ear, with the worse ear used to determine PTA.The main outcome of this study was HRQoL, which was calculated using responses to the 12‐Item Short‐Form Survey (SF‐12), which has been used in previous studies to determine the HRQoL in patients with hearing loss.Lavaan package in R Studio 1.3.1.χ2 test and root mean square error of approximation (RMSEA) statistics in combination with the comparative fit index (CFI) and standardized root mean square residual (SRMR).A priori power analysis was performed using G*Power given the number of variables in the model, the anticipated effect size, and the desired probability to reach the statistical power level of 0.80 (N = 76). Patient characteristics were summarized using descriptive statistics. Once a sample of each categorical variable group was drawn, race was excluded from further analysis because not all groups met the minimum required sample size in each category (n = 5). To evaluate the hypothesized relationships, we performed a path analysis model using the p < .001). Almost half (48%) of the patients had hearing loss on the audiogram. A significantly greater proportion of patients who did not speak English as a primary language had moderate to profound hearing loss compared to patients who spoke English as a primary language . Patients who spoke English as a primary language had a significantly lower proportion of BHL, compared to patients who did not speak English as a primary language . Demographic characteristics from the study sample are presented in Participants were primarily female , non‐Hispanic or Latino , and ranged in age from 18 to 90 (mean age = 54.0 ± 18.4 years) years. Almost one‐third (27.8%) of the patients did not speak English as their primary language . Mean HRQoL was similar between patients who did not speak English as a primary language and patients who spoke English as a primary language (0.75 ± 0.13 vs 0.74 ± 0.12). Regarding hearing levels, PTA scores were significantly higher in patients who did not speak English as a primary language than in patients who spoke English as a primary language , explaining 36.5% of the variance in HRQoL. The total, direct and indirect effects of PTA, hearing loss laterality, age, and primary language on HRQoL are provided in The path model provided an excellent fit  and laterality  had significant direct effects on HRQoL in otology patients, specifically worse hearing and BHL were both associated with lower HRQoL. In our sample, older patients generally reported higher HRQoL . However, aging indirectly affected the relationships between PTA and hearing loss laterality on HRQoL. Namely, older patients with worse hearing had more rapidly declining HRQoL . Similarly, older patients with BHL had more rapidly declining HRQoL than if they had UHL . The number of otologic symptoms and duration of the symptoms did not have significant effects on HRQoL. Male gender was directly positively associated with HRQoL . Patients who spoke English as their primary language reported having significantly worse hearing , but not on laterality. The correlation of aging with increasing PTA was significantly greater in patients who did not speak English as a primary language compared to patients who spoke English as a primary language  (Both PTA (p < .05) .This is the first study to explore the relationship between age, hearing loss, primary language, and HRQoL among otolaryngology patients with otology symptoms. Our findings provide empirical evidence for the hypothesized relationships between age, hearing loss, primary language, and HRQoL. More specifically, this study confirmed that the effect of age on HRQoL is mediated by hearing loss and that primary language is associated with hearing loss and HRQoL.Previous studies have reported that age is one of the strongest predictors of hearing loss prevalence and severity.We found that primary language moderated the relationship between age and hearing loss. Specifically, patients who did not speak English as a primary language exhibited significantly worse hearing and therefore worse HRQoL than English‐speaking patients with hearing loss. These results are consistent with a growing body of evidence that links language barriers to worse health outcomes.While the relationship between primary language and health outcomes has been well‐studied, previous research has done little to investigate how UHL affects health outcomes. In 2018, Golub et al concluded that about 7.2% of adults in the United States suffer from UHL,In our study, polypharmacy was associated with lower HRQoL, which was consistent with previous studies.Gender was another risk factor associated with HRQoL in our analysis. When controlled for age, primary language, and hearing loss severity and laterality, we found that females had worse HRQoL than males, which is consistent with previous literature.The study has several limitations that may prevent generalization beyond our study sample. First, the cross‐sectional nature of the study design limits the determination of causal relationships among study variables. Future research that is longitudinal with attention to understanding the temporal relationships among those variables is indicated. Second, primary language was used as a predicting variable in this study rather than English proficiency, which is a more specific measure of one's ability to understand English. While primary language was self‐reported and determined by which language was utilized during the patient‐physician interaction, some patients who might not be able to interpret more complex medical language may have indicated English as a primary language, thus allowing for errors in interpretation. For patients who did not speak English, a certified translator was used to communicate the instructions for the audiogram prior to the beginning of the test. Consequently, these tests may have been intrinsically biased against patients who did not speak English as a primary language. This study did not document which patients used certified translators during their interaction with the audiologist or physician. Third, our findings pertaining to UHL and BHL were unable to adjust for possible confounding factors such as noise exposure. Lastly, the SF‐12 was administered in English only. For patients who did not speak English as their primary language, response accuracy may be affected. While previous studies have used the SF‐12 to determine HRQoL in patients with hearing loss, the tool's ability to determine the specific effect of hearing loss on HRQoL has yet to be determined.Among patients presenting with otology symptoms, not speaking English as a primary language had a significant interaction with older age, creating a synergistic effect for simultaneously worsening hearing function, which was a significant risk factor for lower subsequent HRQoL. Further research is necessary to evaluate interventions that can adequately address this health disparity in HRQoL among patients who do not speak English as a primary language.Harrison J. Ma, study conception, design, and material preparation, data collection, data analysis and interpretation of data, drafting of the manuscript, revision of manuscript; Francis Reyes Orozco, study conception, design, and material preparation, data collection, revision of manuscript; Christine K. Raj, study conception, design, and material preparation, data collection, revision of manuscript; Kevin Herrera, study conception, design, and material preparation, data collection, revision of manuscript; John C. Parsons, study conception, design, and material preparation, data collection, revision of the manuscript; Ian Kim, study conception, design, and material preparation, data analysis and interpretation of data, drafting of manuscript, revision of manuscript; Kevin Hur, study conception, design, and material preparation, data analysis and interpretation of data, revision of the manuscript, supervision.None.None.