DAC for study Gene Discovery in age related hearing loss
Ontology highlight
ABSTRACT:
PROVIDER: EGAC00001000058 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:The aim is to find new candidate genes associated with progressive hearing loss
| EGAS00001000295 | EGA
Project description:Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive hearing impairment leads to social isolation and is also associated with comorbidities, such as frailty, falls, and late-onset depression. Moreover, there is a growing evidence linking it with cognitive decline and increased risk of dementia. Given the large social and welfare burden that results from ARHL, and because ARHL is potentially a modifiable risk factor for dementia, there is an urgent need for therapeutic interventions to ameliorate age-related auditory decline. However, a prerequisite for design of therapies is knowledge of the underlying molecular mechanisms. Currently, our understanding of ARHL is very limited. Here, we review recent findings from research into ARHL from both human and animal studies and discuss future prospects for advances in our understanding of genetic susceptibility, pathology, and potential therapeutic approaches in ARHL.
| S-EPMC6671929 | biostudies-literature
Project description:BackgroundOur study aimed to determine the pathological mechanism of presbycusis at the molecular level, and determine potential biomarkers for the same.MethodsDifferentially expressed genes (DEGs) for presbycusis were obtained by analyzing the microarray data sets (GSE6045 and GSE49543) downloaded from the Gene Expression Omnibus (GEO). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway, and protein-protein interaction (PPI) network analyses, and Gene Set Enrichment Analysis (GSEA) were performed to analyze the biological functions, molecular pathways, autophagy-related molecular markers, and the immune microenvironment of the DEGs in presbycusis. Then the prognostic roles of the hub genes were analyzed and verified in vivo.ResultsIn the old mild hearing loss group (27.7 ± 3.4 months old), 27 down-regulated and 99 up-regulated genes were significantly differentially expressed compared with those in the young control group (3.5 ± 0.4 months old). In the old severe hearing loss group (30.6 ± 1.9 months old), 131 down-regulated and 89 up-regulated genes were significantly differentially expressed compared with those in the young control group. The results of the GO, GSEA, KEGG pathway, and immune infiltration analyses showed that the enrichment terms were mainly focused on immune response in mild presbycusis, and immune response and cell death in severe presbycusis. In the PPI network, autophagy-related genes ATG5, ATG7 showed the highest node scores in mild presbycusis; whereas MTOR, BECN1 showed the highest scores in severe presbycusis. In the GSE49543 data set, four genes (Ywhag, Mapre2, Fgf1, Acss2) were used to construct the prognostic model, and those four genes were significantly up-regulated in the rat model of presbycusis.ConclusionOur study is the first to report the difference in autophagy factors and immune microenvironment among different degrees of hearing loss in presbycusis. Furthermore, we provide the prognostic gene expression signature for age-related hearing loss, intending to develop preventative therapies.
| S-EPMC9021842 | biostudies-literature
Project description:Hearing loss is a hallmark of aging, typically initially affecting the higher frequencies. In echolocating bats, the ability to discern high frequencies is essential. However, nothing is known about age-related hearing loss in bats, and they are often assumed to be immune to it. We tested the hearing of 47 wild Egyptian fruit bats by recording their auditory brainstem response and cochlear microphonics, and we also assessed the cochlear histology in four of these bats. We used the bats' DNA methylation profile to evaluate their age and found that bats exhibit age-related hearing loss, with more prominent deterioration at the higher frequencies. The rate of the deterioration was ∼1 dB per year, comparable to the hearing loss observed in humans. Assessing the noise in the fruit bat roost revealed that these bats are exposed to continuous immense noise-mostly of social vocalizations-supporting the assumption that bats might be partially resistant to loud noise. Thus, in contrast to previous assumptions, our results suggest that bats constitute a model animal for the study of age-related hearing loss.
| S-EPMC10067528 | biostudies-literature
Project description:ObjectiveTo reveal the relationship between ARHL and ferroptosis and screen ferroptosis-related genes (FRGs) in ARHL.MethodsBioinformatics were used to analyze the hub genes and molecular mechanism of ferroptosis in the aging cochleae. Senescence β-galactosidase staining, iron content detection, and micro malondialdehyde (MDA) assay kits were used to measure β-galactosidase activity, and expression of Fe2+ and MDA, respectively. Fluorescence microscope was used for immunofluorescence assay of hub genes. Western blot was used to verify the expression of hub genes in HEI-OC1 cells, cochlear explants, and cochleae of C57BL/6J mice. Data were expressed as mean ± SD of at least three independent experiments.ResultsThe analysis of bioinformatics confirmed that lactotransferrin (LTF) is the hub gene and CEBPA-miR-130b-LTF network is the molecular mechanism for cochlear ferroptosis. Compared with the control group, the experiments proved that the indicators of ferroptosis, including Fe2+, MDA, and LTF were differentially expressed in aging HEI-OC1 cells, aging cochlear explants, and aging cochleae.ConclusionThese results demonstrate that ferroptosis plays an important role in ARHL, and LTF is a potential therapeutic target for ARHL via regulating cochlear ferroptosis.
| S-EPMC10809180 | biostudies-literature
Project description:Melanoma progression model:DAC-mediated gene expression Keywords: other
2005-07-20 | GSE1793 | GEO
Project description:IntroductionHearing loss is common in ageing populations, but thorough investigation of factors associated with objective hearing loss in otherwise healthy, community-dwelling older individuals is rare. We examined prevalence of age-related hearing loss (ARHL) in healthy, community-dwelling older adults, and determined whether sociodemographic, lifestyle, or health factors associate with hearing thresholds. Audiometry assessment was investigated with self-reports of hearing loss and hearing handicap.MethodsAustralian participants (n = 1,260) of median age 73 years (IQR 71-76) joined ASPirin in Reducing Events in the Elderly (ASPREE)-Hearing, a sub-study of the ASPREE trial with exclusions including cognitive impairment, cardiovascular disease, independence-limiting physical disability, and uncontrolled hypertension. ASPREE collected demographics, anthropometrics, lifestyle, and health data. Audiometry measured better ear pure-tone average (PTA) across four frequencies (0.5-4 kHz) to establish hearing thresholds, categorised as normal or mild, moderate, and severe hearing loss. Questionnaires collected perceived hearing problems and noise exposure.ResultsARHL prevalence by audiometry was 49.7%, affecting men (59%) more than women (41%). A majority (54.5%) self-reported some hearing problems which mostly aligned with objective assessments; 45.6% self-reported a "little trouble" with hearing, while 35% had objective mild hearing loss; 8.3% reported having a "lot of trouble" hearing, while 13% had moderate hearing loss; and 0.6% reported being "deaf," while 2% demonstrated severe hearing loss. There was a significant association (p < 0.001) between self-reported hearing handicap and audiometric measures of hearing loss. In multivariate analysis of health, demographics, and lifestyle risk factors, only age, gender (men), and education years (<12) remained associated (p < 0.05) with hearing loss. Hearing thresholds were not associated with smoking, living situation, alcohol use, hypertension, diabetes, or chronic kidney disease.ConclusionARHL robustly assessed by audiometry is common among healthy older Australians with men more likely to have abnormal hearing thresholds than women. Hearing loss was associated with fewer years of formal education, but not with a range of chronic conditions or alcohol use. Self-reported hearing loss correlates well with higher PTA hearing threshold levels in this healthy cohort where prevalence was lower than previously reported for the age group 70+ years. Hearing health education remains an important public health tool for this age. Targeting hearing in older patient health checks could be beneficial to mitigate the cognitive, social, and mental health consequences of ARHL, even if patients do not report a problem or handicap.
| S-EPMC11854973 | biostudies-literature
Project description:Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. The DBA/2J (DBA) mice have been used as a model of AHL and undergoes progressive, age-related hearing loss by 12 weeks of age. Here we analyzed cochlear gene expression of 7-week-old and 36-week-old DBA mice using microarrays. Auditory brainstem response (ABR) analysis confrimed that severe age-related hearing loss occured in 36-week-old mice, whereas moderate hearing loss occured in 7-week-old mice. Comprehensive gene expression analysis identified genes correlated with AHL and revealeed that 15 mitochondrial process categories, including â??mitochondrial electron transport chainâ??, â??oxidative phosphorylationâ??, â??respiratory chain complex Iâ??, â??respiratory chain complex IVâ??, and â??respiratory chain complex Vâ??, were statistically associated with AHL-correlated genes in the cochlea of 36-week-old DBA mice, and that 25 genes encoding components of the mitochondrial respiratory chain (respiratory chain complex I, IV, and V) were significantly down-regulated in the cochlea. These observations provide evidence that AHL is associated with down-regulation of genes involved in the mitochondrial respiratory chain in the cochlea of DBA mice, and suggest that mitochondrial respiratory chain dysfunction may be a key feature of AHL in mammalian cochlea. Experiment Overall Design: To determine the effects of age-related hearing loss, each 7-week-old sample (n = 3) was compared to each 36-week-old sample (n = 3), generating a total of nine pairwise comparisons. Using DAVIS and EASE, the identified genes were assign to â??GO: Biological Processâ?? categories of Gene Ontology Consortium. Furthermore, we used EASE to determine the total number of genes that were assigned to each biological process category, and to perform Fisher exact test. Quality control measures were not used. No replicates were done. Dye swap was not used.
2008-06-14 | E-GEOD-6045 | biostudies-arrayexpress
Project description:Isocitrate dehydrogenase (IDH) 2 participates in the TCA cycle and catalyzes the conversion of isocitrate to α-ketoglutarate and NADP+ to NADPH. In the mitochondria, IDH2 also plays a key role in protecting mitochondrial components from oxidative stress by supplying NADPH to both glutathione reductase (GSR) and thioredoxin reductase 2 (TXNRD2). Here, we report that loss of Idh2 accelerates age-related hearing loss, the most common form of hearing impairment, in male mice. This was accompanied by increased oxidative DNA damage, increased apoptotic cell death, and profound loss of spiral ganglion neurons and hair cells in the cochlea of 24-month-old Idh2-/- mice. In young male mice, loss of Idh2 resulted in decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the inner ear. In HEI-OC1 mouse inner ear cell lines, knockdown of Idh2 resulted in a decline in cell viability and mitochondrial oxygen consumption. This was accompanied by decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the HEI-OC1 cells. Therefore, IDH2 functions as the principal source of NADPH for the mitochondrial thioredoxin antioxidant defense and plays an essential role in protecting hair cells and neurons against oxidative stress in the cochlea of male mice.
| S-EPMC5864918 | biostudies-literature
Project description:Age-related hearing loss (ARHL) is the most common sensory impairment in the elderly affecting millions of people worldwide. To shed light on the genetics of ARHL, a large cohort of 464 Italian patients has been deeply analyzed at clinical and molecular level.
A missense variant in SLC9A3R1 has been identified in two unrelated ARHL patients. A knock-in zebrafish model confirmed the pathogenic effect of the variant.
| EGAS00001003072 | EGA