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1.
Hear Res ; 446: 109004, 2024 May.
Article En | MEDLINE | ID: mdl-38608332

The naturally occurring amino acid, l-ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, to be utilized by cells as an antioxidant and anti-inflammatory. In our current study, EGT was administered over a period of 6 months to 25-26-month-old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis, and chronic inflammation. Results from the current study indicate that EGT can prevent aging declines of some key features of ARHL. However, we found a distinct sex difference for the response to the treatments, for hearing - Auditory Brainstem Responses (ABRs) and Distortion Product Otoacoustic Emissions (DPOAEs). Males exhibited lower threshold declines in both low dose (LD) and high dose (HD) test groups throughout the testing period and did not display some of the characteristic aging declines in hearing seen in Control animals. In contrast, female mice did not show any therapeutic effects with either treatment dose. Further confirming this sex difference, EGT levels in whole blood sampling throughout the testing period showed greater uptake of EGT in males compared to females. Additionally, RT-PCR results from three tissue types of the inner ear confirmed EGT activity in the cochlea in both males and females. Males and females exhibited significant differences in biomarkers related to apoptosis (Cas-3), inflammation (TNF-a), oxidative stress (SOD2), and mitochondrial health (PGC1a).These changes were more prominent in males as compared to females, especially in stria vascularis tissue. Taken together, these findings suggest that EGT has the potential to be a naturally derived therapeutic for slowing down the progression of ARHL, and possibly other neurodegenerative diseases. EGT, while effective in the treatment of some features of presbycusis in aging males, could also be modified into a general prophylaxis for other age-related disorders where treatment protocols would include eating a larger proportion of EGT-rich foods or supplements. Lastly, the sex difference discovered here, needs further investigation to see if therapeutic conditions can be developed where aging females show better responsiveness to EGT.


Aging , Antioxidants , Cochlea , Disease Models, Animal , Disease Progression , Ergothioneine , Evoked Potentials, Auditory, Brain Stem , Mice, Inbred CBA , Oxidative Stress , Presbycusis , Animals , Ergothioneine/pharmacology , Female , Evoked Potentials, Auditory, Brain Stem/drug effects , Male , Presbycusis/physiopathology , Presbycusis/pathology , Presbycusis/drug therapy , Presbycusis/metabolism , Presbycusis/prevention & control , Oxidative Stress/drug effects , Aging/drug effects , Aging/pathology , Antioxidants/pharmacology , Sex Factors , Cochlea/drug effects , Cochlea/metabolism , Cochlea/physiopathology , Cochlea/pathology , Age Factors , Apoptosis/drug effects , Otoacoustic Emissions, Spontaneous/drug effects , Superoxide Dismutase/metabolism , Auditory Threshold/drug effects , Hearing/drug effects , Mice , Anti-Inflammatory Agents/pharmacology
2.
Hear Res ; 444: 108969, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38350175

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.


Auditory Cortex , Presbycusis , Rats , Animals , Presbycusis/prevention & control , Rats, Wistar , Aging/physiology , Hearing , Evoked Potentials, Auditory, Brain Stem/physiology , Auditory Threshold/physiology
3.
Aging Cell ; 22(9): e13909, 2023 09.
Article En | MEDLINE | ID: mdl-37395319

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.


NAD , Presbycusis , Humans , Animals , Mice , Peroxisome Proliferator-Activated Receptors , Presbycusis/drug therapy , Presbycusis/prevention & control , Cochlea , Dietary Supplements
4.
Exp Gerontol ; 177: 112184, 2023 06 15.
Article En | MEDLINE | ID: mdl-37105504

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.


Presbycusis , Animals , Mice , Disease Models, Animal , Presbycusis/prevention & control , Cochlea , Aging/physiology , Lymphocytes
5.
Acta otorrinolaringol. esp ; 74(2): 124-132, marzo-abril 2023. tab
Article Es | IBECS | ID: ibc-217391

A día de hoy, todavía no disponemos de un conocimiento ni una concienciación adecuados sobre las consecuencias que alcanza en la calidad de vida la pérdida de audición en personas mayores. De la misma manera, tampoco existe información suficiente en cuanto a la relación de la presbiacusia y las alteraciones del equilibrio con otras comorbilidades. Dicho conocimiento puede contribuir a mejorar tanto la prevención como el tratamiento de estas patologías, a reducir su impacto en otras áreas como la cognición o la autonomía, así como para poseer una información más certera sobre el impacto económico que generan en la sociedad y en el sistema sanitario.Por ello, con la realización de este artículo de revisión nos planteamos actualizar la información sobre el tipo de hipoacusia y las alteraciones del equilibrio en personas mayores de 55 años, así como sus factores asociados; analizar el impacto que genera en la calidad de vida de estas personas y el que se puede generar a nivel personal y poblacional (tanto en el ámbito sociológico como económico) si se persigue una intervención temprana en estos pacientes. (AU)


At this time, we still do not have adequate knowledge and awareness of the consequences of hearing loss in the elderly on quality of life. Similarly, there is also insufficient information on the relationship of presbycusis and balance disorders with other comorbidities. Such knowledge can contribute to improve both prevention and treatment of these pathologies, to reduce their impact on other areas such as cognition or autonomy, as well as to have more accurate information on the economic impact they generate in society and in the health system.Therefore, with this review article we aim to update the information on the type of hearing loss and balance disorders in people over 55 years of age, and their associated factors; to analyze the impact on the quality of life of these people and the one which can be generated at a personal and population level (both sociological and economic) if an early intervention in these patients is pursued. (AU)


Humans , Middle Aged , Aged , Aged, 80 and over , Presbycusis , Hearing Loss , Cognition , Otolaryngology , Presbycusis/prevention & control , Hearing Loss/complications , Hearing Loss/therapy
6.
Biochim Biophys Acta Mol Cell Res ; 1869(11): 119331, 2022 11.
Article En | MEDLINE | ID: mdl-35963547

Hearing loss in the elderly cause communication difficulties, decreased quality of life, isolation, loneliness and frustration. The aim of our study was to investigate the effect of drug repurposing candidates in aging mouse. The selected candidate drugs for age-related hearing loss (ARHL) included atorvastatin (AS) and sarpogrelate. Monotherapy or fixed dose combination (FDC) products were administered via oral gavage for 6 consecutive months. Auditory outcomes showed significant hearing preservation in AS-treated aging mice compared to aging control, especially in the early stages of ARHL in both 8 and 16 kHz frequencies. However, none of the FDC products were able to prevent ARHL regardless of AS involvement. In aging mice, damage and dysfunction of mitochondria was noted as well as reactive oxygen species overproduction leading to oxidative stress and intrinsic apoptosis. These processes of ARHL were significantly prevented with administration of AS. Normal structures of mitochondria were maintained, and antioxidant activity were proceeded by activation of HSF1/Sirt1 pathway. Our study suggests that AS is a promising drug repurposing candidate to delay the progression of ARHL.


Hydroxymethylglutaryl-CoA Reductase Inhibitors , Presbycusis , Animals , Drug Repositioning , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Mice , Oxidative Stress , Presbycusis/drug therapy , Presbycusis/prevention & control , Quality of Life
7.
Braz J Otorhinolaryngol ; 88 Suppl 3: S103-S108, 2022.
Article En | MEDLINE | ID: mdl-35780011

OBJECTIVE: The present study aimed to perform a morphological and morphometric analysis of cochlear structures of C57BL/6J mice receiving oral melatonin for a 12-month period. METHODS: 32 male C57BL/6J were divided into control and melatonin groups. Control received saline and ethanol solution and melatonin group, 50 µL of 10 mg of melatonin/kg/day orally for a 12-month period. After de experiment the animals were sacrificed into a 40% concentration of CO2 chamber, and the blades were morphological and morphometrically analyzed. RESULTS: The melatonin group revealed a higher median density of viable cells (45 ±â€¯10.28 cells/100 µm2, 31-73, vs. 32 ±â€¯7.47 cells/100 µm2, 25-48). The median area of stria vascularis was 55.0 ±â€¯12.27 cells/100 µm2 (38-80) in the control, and 59.0 ±â€¯16.13 cells/100 µm2 (40-134) in the melatonin group. The morphometric analysis of the spiral ligament reveals a higher median of total viable neurons in the melatonin (41 ±â€¯7.47 cells/100 µm2, 27-60) than in the control group (31 ±â€¯5.68 cells/100 µm2, 21-44). CONCLUSION: Although melatonin is a potent antioxidant, it does not completely neutralize the occurrence of presbycusis; however, it may delay the onset of this condition.


Melatonin , Presbycusis , Mice , Animals , Male , Presbycusis/prevention & control , Melatonin/pharmacology , Mice, Inbred C57BL , Stria Vascularis , Models, Theoretical
8.
Exp Gerontol ; 155: 111552, 2021 11.
Article En | MEDLINE | ID: mdl-34530105

Age-related hearing loss (ARHL) is sensory impairment in the elderly. This study aimed to identify a critical molecular mechanism that can maintain young phenotypes. We focused on the effect of exposure to environmental enrichment (EE) for 12 weeks in the central auditory pathway and limbic system of aged rats. The effects of EE were compared with the effects of dexamethasone administration. We found that in 74-week-old rats hearing function was significantly reduced and the number of neuronal specific nuclear protein (NeuN)-positive cells was decreased by 10-15% in the auditory cortex, amygdala, and hippocampus. EE exposure did not significantly affect the number of neurons, but DX administration significantly decreased their numbers in the amygdala compared with untreated aged rats. Both treatments reduced inducible nitric oxide synthase (iNOS) expression in the auditory pathway and limbic system. Exposure to EE significantly increased silent information regulator 1 (SIRT1) expression and activity, and nicotinamide phosphoribosyltransferase (NAMPT) concentration. In this study, the exposure to EE resulted in attenuated age-related hearing loss accompanied by reduction of iNOS expression and increase SIRT1 activity and NAMPT level. These data showed that EE may be a potential therapeutic to prevent ARHL.


Auditory Cortex , Presbycusis , Sirtuin 1 , Aging , Animals , Auditory Cortex/metabolism , Environment , Hippocampus/metabolism , Presbycusis/prevention & control , Rats , Sirtuin 1/metabolism
9.
Cells ; 10(9)2021 09 17.
Article En | MEDLINE | ID: mdl-34572102

Endoplasmic reticulum (ER) stress is a common stress factor during the aging process. Heat shock factor 1 (HSF1) plays a critical role in ER stress; however, its exact function in age-related hearing loss (ARHL) has not been fully elucidated. The purpose of the present study was to identify the role of HSF1 in ARHL. In this study, we demonstrated that the loss of inner and outer hair cells and their supporting cells was predominant in the high-frequency region (basal turn, 32 kHz) in ARHL cochleae. In the aging cochlea, levels of the ER stress marker proteins p-eIF2α and CHOP increased as HSF1 protein levels decreased. The levels of various heat shock proteins (HSPs) also decreased, including HSP70 and HSP40, which were markedly downregulated, and the expression levels of Bax and cleaved caspase-3 apoptosis-related proteins were increased. However, HSF1 overexpression showed significant hearing protection effects in the high-frequency region (basal turn, 32 kHz) by decreasing CHOP and cleaved caspase-3 and increasing the HSP40 and HSP70 proteins. These findings were confirmed by HSF1 functional studies using an auditory cell model. Therefore, we propose that HSF1 can function as a mediator to prevent ARHL by decreasing ER stress-dependent apoptosis in the aging cochlea.


Apoptosis , Endoplasmic Reticulum Stress , Heat Shock Transcription Factors/metabolism , Presbycusis/prevention & control , Unfolded Protein Response , Animals , Caspase 3/genetics , Caspase 3/metabolism , Cochlea/metabolism , Cochlea/pathology , Heat Shock Transcription Factors/genetics , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Male , Mice , Mice, Inbred C57BL , Presbycusis/etiology , Presbycusis/metabolism , Presbycusis/pathology
10.
Neural Plast ; 2021: 9979157, 2021.
Article En | MEDLINE | ID: mdl-34194490

Hearing loss is a debilitating disease that affects 10% of adults worldwide. Most sensorineural hearing loss is caused by the loss of mechanosensitive hair cells in the cochlea, often due to aging, noise, and ototoxic drugs. The identification of genes that can be targeted to slow aging and reduce the vulnerability of hair cells to insults is critical for the prevention of sensorineural hearing loss. Our previous cell-specific transcriptome analysis of adult cochlear hair cells and supporting cells showed that Clu, encoding a secreted chaperone that is involved in several basic biological events, such as cell death, tumor progression, and neurodegenerative disorders, is expressed in hair cells and supporting cells. We generated Clu-null mice (C57BL/6) to investigate its role in the organ of Corti, the sensory epithelium responsible for hearing in the mammalian cochlea. We showed that the deletion of Clu did not affect the development of hair cells and supporting cells; hair cells and supporting cells appeared normal at 1 month of age. Auditory function tests showed that Clu-null mice had hearing thresholds comparable to those of wild-type littermates before 3 months of age. Interestingly, Clu-null mice displayed less hair cell and hearing loss compared to their wildtype littermates after 3 months. Furthermore, the deletion of Clu is protected against aminoglycoside-induced hair cell loss in both in vivo and in vitro models. Our findings suggested that the inhibition of Clu expression could represent a potential therapeutic strategy for the alleviation of age-related and ototoxic drug-induced hearing loss.


Clusterin/deficiency , Hair Cells, Auditory/physiology , Hearing Loss, Sensorineural/prevention & control , Presbycusis/prevention & control , Animals , Auditory Threshold , Base Sequence , CRISPR-Cas Systems , Cellular Senescence , Clusterin/biosynthesis , Clusterin/genetics , Clusterin/physiology , Drug Synergism , Evoked Potentials, Auditory, Brain Stem , Furosemide/administration & dosage , Furosemide/toxicity , Hair Cells, Auditory/drug effects , Hearing Loss, Sensorineural/chemically induced , Kanamycin/administration & dosage , Kanamycin/toxicity , Mice , Mice, Inbred C57BL , Mice, Knockout , Organ Culture Techniques , Organ of Corti/pathology , Otoacoustic Emissions, Spontaneous , RNA, Messenger/biosynthesis , RNA, Messenger/genetics
11.
J Neuroimmunol ; 357: 577628, 2021 08 15.
Article En | MEDLINE | ID: mdl-34130076

We investigated the association between cellular immunity and age-related hearing loss (ARHL) development using three CD4+ T cell fractions, namely, naturally occurring regulatory T cells (Treg), interleukin 1 receptor type 2-expressing T cells (I1R2), and non-Treg non-I1R2 (nTnI) cells, which comprised Treg and I1R2-deleted CD4+ T cells. Inoculation of the nTnI fraction into a ARHL murine model, not only prevented the development of ARHL and the degeneration of spiral ganglion neurons, but also suppressed serum nitric oxide, a source of oxidative stress. Further investigations on CD4+ T cell fractions could provide novel insights into the prevention of aging, including presbycusis.


CD4-Positive T-Lymphocytes/transplantation , Presbycusis/immunology , Presbycusis/prevention & control , T-Lymphocyte Subsets/transplantation , Animals , CD4-Positive T-Lymphocytes/immunology , Disease Models, Animal , Disease Progression , Mice , Receptors, Interleukin-1 Type II/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology
12.
Aging Cell ; 19(12): e13275, 2020 12.
Article En | MEDLINE | ID: mdl-33222382

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL+ apoptotic cells were all lower in 9-month-old G6PD-Tg than in wild-type counterparts. Unexpectedly, G6PD overexpression triggered low-grade inflammation that was effectively resolved in young mice, as shown by the absence of cochlear cellular damage and macrophage infiltration. Our results lead us to propose that NADPH overproduction from an early stage is an efficient mechanism to maintain the balance between the production of ROS and cellular detoxification power along aging and thus prevents hearing loss progression.


Aging/metabolism , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase/metabolism , Presbycusis/enzymology , Presbycusis/prevention & control , Aging/physiology , Animals , Apoptosis , Auditory Threshold/physiology , Cochlea/metabolism , Cochlea/pathology , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , NADP/biosynthesis , Oxidative Stress , Presbycusis/physiopathology , Reactive Oxygen Species/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Up-Regulation
13.
Proc Natl Acad Sci U S A ; 117(21): 11811-11819, 2020 05 26.
Article En | MEDLINE | ID: mdl-32393641

"Growing old" is the most common cause of hearing loss. Age-related hearing loss (ARHL) (presbycusis) first affects the ability to understand speech in background noise, even when auditory thresholds in quiet are normal. It has been suggested that cochlear denervation ("synaptopathy") is an early contributor to age-related auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calcium-gated potassium channels. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses. Cochlear structure was characterized in immunolabeled organ of Corti whole mounts using confocal microscopy to quantify hair cells, auditory neurons, presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost from inner hair cells throughout the aged cochlea, together with some loss of outer hair cells. In contrast, cochlear structure and function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochlear inhibition, suggesting that efferent feedback is important for long-term maintenance of inner ear function. Our work provides evidence that olivocochlear-mediated resistance to presbycusis-ARHL occurs via the α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.


Aging/physiology , Cochlea , Hair Cells, Auditory, Outer , Presbycusis , Superior Olivary Complex , Animals , Cochlea/physiology , Cochlea/physiopathology , Evoked Potentials, Auditory, Brain Stem/physiology , Feedback, Physiological/physiology , Hair Cells, Auditory, Outer/cytology , Hair Cells, Auditory, Outer/physiology , Mice , Otoacoustic Emissions, Spontaneous/physiology , Presbycusis/physiopathology , Presbycusis/prevention & control , Superior Olivary Complex/cytology , Superior Olivary Complex/physiology
14.
Hear Res ; 389: 107926, 2020 04.
Article En | MEDLINE | ID: mdl-32101784

C57BL/6J mice have long been studied as a model of age-related hearing loss (ARHL). In C57BL/6J mice, ARHL begins in the high-frequency range at 3 months of age and spreads toward low frequencies by 10 months of age. We previously confirmed that c.753A>G genome editing of an ahl allele (c.753A) in the cadherin 23 gene (Cdh23) suppressed the onset of ARHL until 12 months of age. We further investigated the hearing phenotypes of the original and genome-edited C57BL/6J-Cdh23+/+ (c.753G/G) mice until 24 months of age. The hearing tests revealed that most of the C57BL/6J mice maintained good hearing levels until 14 months of age following genome editing of a Cdh23ahl allele. However, the hearing levels of the C57BL/6J-Cdh23+/+ mice gradually declined, and severe ARHL developed with increasing age. ARHL in the C57BL/6J mice was correlated with degeneration of the stereocilia in cochlear hair cells. The stereocilia degeneration was rescued in the C57BL/6J-Cdh23+/+ mice at 12 months of age, but the stereocilia bundles exhibited abnormal phenotypes similar to those of the original C57BL/6J mice at more advanced ages. Therefore, genome editing of Cdh23ahl did not completely suppress ARHL in C57BL/6J mice. We also compared the hearing levels of C57BL/6J-Cdh23+/+ mice with those of C3H/HeN and MSM/Ms mice, which carry the Cdh23+ allele. The severity and onset patterns of ARHL in the C57BL/6J-Cdh23+/+ mice differed from those observed in other Cdh23+/+ mice. Therefore, we hypothesize that other susceptible and/or resistant alleles of ARHL exist in the genetic backgrounds of these mice.


Cadherins/genetics , Gene Editing , Genetic Therapy , Hair Cells, Auditory/ultrastructure , Hearing , Mutation , Presbycusis/prevention & control , Age Factors , Animals , Auditory Threshold , Cadherins/metabolism , Disease Models, Animal , Evoked Potentials, Auditory, Brain Stem , Genetic Predisposition to Disease , Hair Cells, Auditory/metabolism , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic , Otoacoustic Emissions, Spontaneous , Phenotype , Presbycusis/genetics , Presbycusis/metabolism , Presbycusis/pathology
15.
PLoS One ; 15(2): e0228943, 2020.
Article En | MEDLINE | ID: mdl-32040524

INTRODUCTION: Age-related hearing loss (ARHL) is a consequence of aging of the auditory system. The best known mechanism of cell death in ARHL is apoptosis due to increased production of reactive oxygen species. In this context, it is hypothesized that melatonin, owing to its high antioxidant potential and its action in the mitochondria, helps prevent or delay outer hair cell dysfunction (HCD). AIMS: To evaluate the effect of melatonin on the prevention of HCD dysfunction in the ARHL process in a susceptible murine C57BL/6J model. METHOD: C57BL/6J animals were divided into two groups: control (CG) and melatonin (MG). The CG received a saline and ethanol solution and the MG, melatonin (10 mg/kg/day). The solutions were offered daily (50 µl) orally over a 10-month period. Distortion Product Otoacoustic Emissions (DPOAE) measurements were conducted once a month. RESULTS: There was a decrease in DPOAE values in both groups over time and a differentiation between them from the 10th month of life onwards. At 10 months, the MG maintained higher DPOAE values than the CG at all frequencies tested. CONCLUSION: The use of melatonin has otoprotective effects on HCD in the ARHL process in the C57BL/6J model.


Melatonin/administration & dosage , Presbycusis/prevention & control , Administration, Oral , Animals , Antioxidants/administration & dosage , Cadherins/genetics , Disease Models, Animal , Hair Cells, Auditory/drug effects , Male , Mice , Mice, Inbred C57BL , Mutation, Missense , Otoacoustic Emissions, Spontaneous/drug effects , Presbycusis/genetics , Presbycusis/physiopathology
16.
Nutrients ; 12(2)2020 Feb 07.
Article En | MEDLINE | ID: mdl-32046004

Age related hearing loss (ARHL) affects about one third of the elderly population. It is suggested that the senescence of the hair cells could be modulated by inflammation. Thus, intake of anti- and pro-inflammatory foods is of high interest. METHODS: From the MICOL study population, 734 participants were selected that participated in the 2013 to 2018 examination including hearing ability and from which past data collected in 2005/2008 was available. ARHL status was determined and compared cross-sectionally and retrospectively according to clinical and lifestyle data including food and micronutrient intake. RESULTS: ARHL status was associated with higher age but not with education, smoking, relative weight (BMI), and clinical-chemical blood markers in the crossectional and retrospective analyses. Higher intake of fruit juices among ARHL-participants was seen cross-sectionally, and of sugary foods, high-caloric drinks, beer, and spirits retrospectively. No difference was found for the other 26 food groups and for dietary micronutrients with the exception of past vitamin A, which was higher among normal hearing subjects. CONCLUSIONS: Pro-inflammatory foods with a high-sugar content and also beer and spirits were found to be assocated with positive ARHL-status, but not anti-inflammatory foods. Diet could be a candidate for lifestyle advice for the prevention of ARHL.


Alcoholic Beverages/adverse effects , Diet, Carbohydrate Loading/adverse effects , Eating , Life Style , Presbycusis/etiology , Presbycusis/prevention & control , Risk Reduction Behavior , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Italy , Male , Middle Aged , Retrospective Studies , Socioeconomic Factors
17.
Adv Exp Med Biol ; 1130: 59-71, 2019.
Article En | MEDLINE | ID: mdl-30915701

Presbycusis is a sensorineural hearing loss caused by hearing system aging and degeneration. The clinical manifestations are progressive bilateral symmetrical hearing loss, and the hearing curve is mostly slope-shaped with high-frequency reduction, sometimes flat. The results of the second national sample survey of disabled persons (2006) showed that the total number of hearing and speech disability in China was 27.8 million, accounting for 34% of the total number of disabled people in China. Among them are people over 60 years old. There are 20.4541 million people with hearing disabilities. There are 9.49 million senile deaf patients, accounting for 34.1% of the total number of hearing disabilities. As society gradually becomes aging, the incidence of presbycusis is getting higher and higher. The study of its pathogenesis is of great significance for the diagnosis, treatment, and prevention of presbycusis. The rapid progress of molecular biology experimental technology has provided us with a new opportunity to fully understand and reveal the presbycusis. In the near future, early diagnosis of presbycusis-related genes and early prevention or delay of the occurrence and development of presbycusis will become a reality.


Hearing Loss, Sensorineural/prevention & control , Presbycusis/prevention & control , China , Humans
18.
Hear Res ; 370: 11-15, 2018 12.
Article En | MEDLINE | ID: mdl-30245283

Adding rapamycin or acarbose to diet at 9-10 months of age has been shown to significantly increase life span in both male and female UM-HET3 mice. The current study examined cochleae of male and female UM-HET3 mice at 22 months of age to determine if either treatment also influenced age-related loss of cochlear hair cells. A large loss of cochlear outer hair cells was observed at 22 months of age in untreated mice in both apical and basal halves of the cochlear spiral. Addition of acarbose to diet had no significant effect on the amount of outer hair cell loss at 22 months of age or in its pattern, with large loss in both apical and basal halves. The addition of rapamycin to diet, however, significantly reduced outer hair cell loss in the basal half of the cochlea at 22 months of age when compared to untreated mice. There was no significant difference between male and female mice in any of the conditions. Age-related outer hair cell loss in the apical cochlea precedes outer hair cell loss in the base in many mouse strains. The results of the present study suggest that rapamycin but not acarbose treatment can delay age-related loss of outer hair cells at doses at which each drug increases life span.


Acarbose/pharmacology , Hair Cells, Auditory, Outer/drug effects , Hearing/drug effects , Presbycusis/prevention & control , Sirolimus/pharmacology , Age Factors , Animals , Cell Death/drug effects , Cytoprotection , Disease Models, Animal , Female , Genetic Predisposition to Disease , Hair Cells, Auditory, Outer/pathology , Hearing/genetics , Male , Mice, Transgenic , Phenotype , Presbycusis/genetics , Presbycusis/pathology , Presbycusis/physiopathology
19.
Biogerontology ; 19(2): 159-169, 2018 04.
Article En | MEDLINE | ID: mdl-29363005

Dietary antioxidants, polyphenols, have been found to be beneficial in protecting against the generation of oxidative stress in various diseases associated with aging. Age-related hearing loss (AHL) is the number one neurodegenerative disorder on our aged population. Sprague-Dawley rats divided into five groups according to their age (3, 6, 12, 18 and 24 months old) and treated with 100 mg/day/kg body weight of polyphenols were used. Then, cochleae were harvested to measure caspase activities (- 3, - 8 and - 9), caspase-3 gene expression, ATP levels, Bax, BcL-2 and p53 levels. 8-OHdG levels (marker of DNA oxidative damage) and annexin-V were also measured in cochleae. Increased levels of caspase-3 and 9 in cochlea were observed with age and this effect was attenuated by polyphenol treatment. In addition, ATP and Bcl-2 levels in older rats were recovered after administration of polyphenols, while Bax and p53 levels protein decreased. Oral supplementation with polyphenols also reduces DNA oxidative damage of cochlear cell. Treatment with polyphenols inhibits the activation of age-related apoptotic signaling by decreasing oxidative stress inside the rat cochlea.


Aging/drug effects , Cochlea/drug effects , Polyphenols/pharmacology , 8-Hydroxy-2'-Deoxyguanosine , Adenosine Triphosphate/metabolism , Aging/metabolism , Aging/pathology , Animals , Annexin A5/metabolism , Antioxidants/pharmacology , Apoptosis/drug effects , Caspase 3/metabolism , Cochlea/metabolism , Cochlea/pathology , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Disease Models, Animal , Female , Humans , Oxidative Stress/drug effects , Presbycusis/metabolism , Presbycusis/pathology , Presbycusis/prevention & control , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Tumor Suppressor Protein p53/metabolism
20.
Audiol., Commun. res ; 23: e1867, 2018. tab, graf
Article Pt | LILACS | ID: biblio-888393

RESUMO Introdução Aparelhos portáteis realizam triagem que identifica possíveis alterações auditivas, permitindo maior número de beneficiados. Além disso, questionários de autoavaliação podem oferecer panorama da percepção que o idoso tem do seu problema. Objetivo Verificar se os resultados da triagem auditiva em idosos se relacionam com a percepção da restrição de participação social e se existe influência da idade, gênero e escolaridade, nas variáveis. Métodos Estudo transversal realizado com idosos em dois centros de convivência. Foi realizada uma anamnese, em que constavam dados de identificação, idade e escolaridade. Foi realizada a inspeção visual do meato acústico externo e, em seguida, a triagem auditiva, utilizando equipamento portátil. Em forma de entrevista, aplicou-se o questionário Hearing Handicap Inventory for the Elderly - Screening Version (HHIE-S), constituído de 10 questões e dividido em duas escalas, a social e a emocional, cada uma composta de cinco questões. Os dados foram tabulados e analisados estatisticamente. Resultados Foram avaliados 64 idosos, de ambos os gêneros, com média de idade de 70 anos e 8 meses. Destes, 48 (75%) apresentaram-se sem percepção de restrição, 12 (18,75%), com percepção leve a moderada e quatro (6,25%), com percepção significante, segundo classificação do questionário. Os resultados da triagem e do questionário não foram influenciados pelo gênero e pela escolaridade. A idade também não influenciou a pontuação do questionário, porém, houve associação da idade com a triagem e também houve associação entre a triagem auditiva e o questionário. Conclusão Idosos que "falharam" na triagem auditiva apresentaram maior pontuação no questionário e idosos mais velhos apresentaram piores resultados na triagem auditiva.


ABSTRACT Introduction Portable equipment can now perform screenings that identify possible hearing loss, allowing a greater number of people to be evaluated. Self-assessment questionnaires may also provide an overview of the elderly's perception of their problem. Purpose To examine if the hearing-screening results in the elderly are related to their perceived restriction in social participation, and whether they are influenced by age, gender and schooling. Methods A cross-sectional study was carried out with elderly people of two cohabitation centers. Medical history and participant details were collected, including name, age, and schooling data. Visual inspection of the external auditory meatus and hearing screening using portable equipment were then performed. The Hearing Handicap Inventory for the Elderly - Screening Version (HHIE-S) questionnaire was then administered in the form of an interview. The HHIE-S consists of ten questions divided into two scales—social and emotional - each composed of five questions. The data were then statistically analyzed. Results Sixty-four elderly people, comprising men and women, with a mean age of 70 years and 8 months, were evaluated. Of these, 48 (75%) were classified as without perceived restriction, 12 (18.75%) with mild to moderate perceived restriction, and four (6.25%) with significant perceived restriction, according to the questionnaire criteria. The screening and questionnaire results were not influenced by gender and schooling. Age did not influence the questionnaire score, but was associated with the hearing-screening outcome. There was a relationship between hearing screening and scores on the questionnaire. Conclusion Elderly patients who "failed" the hearing screening had higher scores in the questionnaire and older adults had worse hearing-screening results.


Humans , Middle Aged , Aged , Aged, 80 and over , Hearing Loss, Sensorineural/prevention & control , Presbycusis/prevention & control , Social Isolation , Triage , Audiometry , Cross-Sectional Studies , Health of the Elderly , Mass Screening
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