{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:30:46Z","timestamp":1762151446317,"version":"build-2065373602"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Age-related hearing loss (ARHL) is a common chronic condition that significantly affects the quality of life in older adults. Studies have shown that genetic factors play a substantial role in ARHL, with heritability estimates ranging from 46 to 74%. Although advances in genomics and epigenetics have led to the identification of numerous candidate genes in recent years, most related studies have focused on European and North American populations. There remains a lack of systematic mapping of research trends and cross-ethnic gene consistency, limiting the broad applicability of these findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This study screened English-language publications on ARHL genetics from 1995 to June 2025 across PubMed, Embase, Web of Science, and Scopus, ultimately including 465 studies. Bibliometric analyses were conducted using R Bibliometrix, VOSviewer, and CiteSpace to extract research trends, research hotspots, and candidate genes. Ethnic information from human studies were compiled to facilitate cross-ethnic comparative analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      Over the past 30 years, publications in this field have shown continuous growth, with an average annual growth rate of 6.83%. Hearing Research emerged as the core journal. China and the United States were the top two publishing countries, though international collaboration remained limited. Research priorities have gradually shifted from inner ear anatomy to molecular mechanisms such as gene variants, oxidative stress, mitochondrial function, and inflammation. A total of 365 candidate factors from animal studies and 221 candidate genes from human studies were extracted and grouped into seven categories. Cross-ethnic analysis identified 56 genes that were repeatedly reported across at least two populations. Among these,\n                      <jats:italic>CDH23<\/jats:italic>\n                      ,\n                      <jats:italic>ILDR1<\/jats:italic>\n                      , and\n                      <jats:italic>SLC26A5<\/jats:italic>\n                      showed high cross-ethnic consistency, while genes such as\n                      <jats:italic>GRHL2<\/jats:italic>\n                      exhibited notable ethnic specificity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study systematically maps the developmental trajectory and research hotspots of ARHL genetics, revealing key patterns in geographic distribution, thematic evolution, and cross-ethnic applicability. The findings highlight the urgent need to strengthen research in non-European populations and promote international collaboration, thereby providing a theoretical foundation and data support for building a universally applicable genetic risk framework and advancing individualised interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2025.1678115","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:24:54Z","timestamp":1762151094000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From genomic discovery to application in age-related hearing loss: a global bibliometric and cross-ethnic analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ka Ho Kairos","family":"Sou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuoyuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Uus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41514-021-00069-4","article-title":"Hearing difficulty is linked to Alzheimer\u2019s disease by common genetic vulnerability, not shared genetic architecture.","volume":"7","author":"Abidin","year":"2021","journal-title":"NPJ Aging Mech. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1086\/375122","article-title":"Mutations of MYO6 are associated with recessive deafness, DFNB37.","volume":"72","author":"Ahmed","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.fsigen.2006.09.001","article-title":"Coding region mitochondrial DNA SNPs: Targeting East Asian and Native American haplogroups.","volume":"1","author":"Alvarez-Iglesias","year":"2007","journal-title":"Forensic Sci. Int. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/j.joi.2017.08.007","article-title":"bibliometrix: An R-tool for comprehensive science mapping analysis.","volume":"11","author":"Aria","year":"2017","journal-title":"J. Informetr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6158","DOI":"10.3390\/ijms22116158","article-title":"Roles of key ion channels and transport proteins in age-related hearing loss.","volume":"22","author":"Bazard","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1534\/genetics.105.043075","article-title":"Haplotype diversity in 11 candidate genes across four populations.","volume":"171","author":"Beaty","year":"2005","journal-title":"Genetics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3389\/fnagi.2018.00241","article-title":"CDH23 methylation status and presbycusis risk in elderly women.","volume":"10","author":"Bouzid","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"a033217","DOI":"10.1101\/cshperspect.a033217","article-title":"Age-Related hearing loss.","volume":"9","author":"Bowl","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1109\/TKDE.2007.190689","article-title":"On modularity clustering.","volume":"20","author":"Brandes","year":"2008","journal-title":"IEEE Trans. Knowl. Data Eng."},{"key":"B10","doi-asserted-by":"publisher","first-page":"20007","DOI":"10.1038\/s41598-022-24365-5","article-title":"Variant brain-derived neurotrophic factor val66met polymorphism engages memory-associated systems to augment olfaction.","volume":"12","author":"Chao","year":"2022","journal-title":"Sci. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.schres.2020.06.019","article-title":"A polymorphism in the glutamate metabotropic receptor 7 is associated with cognitive deficits in the early phases of psychosis.","volume":"249","author":"Chaumette","year":"2022","journal-title":"Schizophr. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1515\/jdis-2017-0006","article-title":"Science mapping: A systematic review of the literature.","volume":"2","author":"Chen","year":"2017","journal-title":"J. Data Inf. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1605","DOI":"10.1038\/cddis.2014.549","article-title":"Bmi1 regulates auditory hair cell survival by maintaining redox balance.","volume":"6","author":"Chen","year":"2015","journal-title":"Cell Death Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/s41431-025-01789-x","article-title":"Mendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis.","volume":"33","author":"Cornejo-Sanchez","year":"2025","journal-title":"Eur. J. Hum. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/s41431-023-01302-2","article-title":"Rare-variant association analysis reveals known and new age-related hearing loss genes.","volume":"31","author":"Cornejo-Sanchez","year":"2023","journal-title":"Eur. J. Hum. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.gene.2012.01.042","article-title":"SIRT3 gene expression: A link between inherited mitochondrial DNA variants and oxidative stress.","volume":"497","author":"D\u2019Aquila","year":"2012","journal-title":"Gene"},{"key":"B17","doi-asserted-by":"publisher","first-page":"S256","DOI":"10.1093\/geront\/gnw033","article-title":"Aging and hearing health: The life-course approach.","volume":"56","author":"Davis","year":"2016","journal-title":"Gerontologist"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1002\/1873-3468.14671","article-title":"Cytochrome c oxidase biogenesis - from translation to early assembly of the core subunit COX1.","volume":"597","author":"Dennerlein","year":"2023","journal-title":"FEBS Lett."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1002\/2211-5463.13382","article-title":"ISG20: An enigmatic antiviral RNase targeting multiple viruses.","volume":"12","author":"Deymier","year":"2022","journal-title":"FEBS Open Bio"},{"key":"B20","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1007\/s10162-007-0089-4","article-title":"Conservation of hearing by simultaneous mutation of Na,K-ATPase and NKCC1.","volume":"8","author":"Diaz","year":"2007","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1097\/AUD.0000000000000610","article-title":"Heritability of age-related hearing loss in middle-aged and elderly Chinese: A population-based twin study.","volume":"40","author":"Duan","year":"2019","journal-title":"Ear. Hear."},{"key":"B22","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1023\/A:1009820201126","article-title":"Benchmarking Kappa: Interrater agreement in software process assessments.","volume":"4","author":"El Emam","year":"1999","journal-title":"Empir. Softw. Eng."},{"key":"B23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s12041-022-01416-4","article-title":"Imputation of SNPs associated with presbycusis through linkage disequilibrium analysis in the ILDR1 gene.","volume":"102","author":"Flores","year":"2023","journal-title":"J. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.3390\/genes11111260","article-title":"5HTTLPR genetic variant and major depressive disorder: A review.","volume":"11","author":"Fratelli","year":"2020","journal-title":"Genes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1093\/hmg\/ddn402","article-title":"GRM7 variants confer susceptibility to age-related hearing impairment.","volume":"18","author":"Friedman","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1042\/BCJ20200799","article-title":"Weakening of interaction networks with aging in tip-link protein induces hearing loss.","volume":"478","author":"Garg","year":"2021","journal-title":"Biochem. J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1038\/s41598-017-01142-3","article-title":"Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure.","volume":"7","author":"Gilels","year":"2017","journal-title":"Sci. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1038\/s41598-024-83428-x","article-title":"Bioinformatics approach reveals the critical role of inflammation-related genes in age-related hearing loss.","volume":"15","author":"Gu","year":"2025","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"146918","DOI":"10.1016\/j.gene.2022.146918","article-title":"Genome-wide DNA methylation analysis of middle-aged and elderly monozygotic twins with age-related hearing loss in Qingdao. China.","volume":"849","author":"Guo","year":"2023","journal-title":"Gene"},{"key":"B30","doi-asserted-by":"publisher","first-page":"21420","DOI":"10.1038\/s41598-024-71774-9","article-title":"The biphasic impact of apolipoprotein E \u03b54 allele on age-related hearing loss.","volume":"14","author":"Han","year":"2024","journal-title":"Sci. Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1080\/15476278.2018.1462433","article-title":"Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells.","volume":"14","author":"Han","year":"2018","journal-title":"Organogenesis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e310502","DOI":"10.3145\/epi.2022.sep.02","article-title":"SCImago Graphica: A new tool for exploring and visually communicating data.","volume":"31","author":"Hassan-Montero","year":"2022","journal-title":"Prof. Inf."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e1006371","DOI":"10.1371\/journal.pgen.1006371","article-title":"A large genome-wide association study of age-related hearing impairment using electronic health records.","volume":"12","author":"Hoffmann","year":"2016","journal-title":"PLoS Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13020-023-00825-6","article-title":"Age-related hearing loss and its potential drug candidates: A systematic review.","volume":"18","author":"Hu","year":"2023","journal-title":"Chin. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s10571-025-01592-8","article-title":"The role of estrogen in mitochondrial disease.","volume":"45","author":"Huang","year":"2025","journal-title":"Cell Mol. Neurobiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1177\/0194599812446904","article-title":"Association of cadherin23 single nucleotide polymorphism with age-related hearing impairment in Han Chinese.","volume":"147","author":"Hwang","year":"2012","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"B37","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/s42003-021-02224-9","article-title":"The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis.","volume":"4","author":"Ivarsdottir","year":"2021","journal-title":"Commun. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1093\/gerona\/glab378","article-title":"Sex difference and interaction of SIRT1 and FOXO3 candidate longevity genes on life expectancy: A 10-year prospective longitudinal cohort study.","volume":"77","author":"Ji","year":"2022","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.ygeno.2008.06.007","article-title":"A locus on distal chromosome 11 (ahl8) and its interaction with Cdh23 ahl underlie the early onset, age-related hearing loss of DBA\/2J mice.","volume":"92","author":"Johnson","year":"2008","journal-title":"Genomics"},{"key":"B40","doi-asserted-by":"publisher","first-page":"44450","DOI":"10.1038\/srep44450","article-title":"Effects of Cdh23 single nucleotide substitutions on age-related hearing loss in C57BL\/6 and 129S1\/Sv mice and comparisons with congenic strains.","volume":"7","author":"Johnson","year":"2017","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.heares.2010.11.002","article-title":"Hearing and vestibular deficits in the Coch(-\/-) null mouse model: Comparison to the Coch(G88E\/G88E) mouse and to DFNA9 hearing and balance disorder.","volume":"272","author":"Jones","year":"2011","journal-title":"Hear Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s12916-024-03364-5","article-title":"Association between genetic risk and adherence to healthy lifestyle for developing age-related hearing loss.","volume":"22","author":"Jung","year":"2024","journal-title":"BMC Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"367","DOI":"10.3390\/brainsci10060367","article-title":"Silence, solitude, and serotonin: Neural mechanisms linking hearing loss and social isolation.","volume":"10","author":"Keesom","year":"2020","journal-title":"Brain Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1002\/jnr.24439","article-title":"Pathology and mechanisms of cochlear aging.","volume":"98","author":"Keithley","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0378-5955(03)00365-4","article-title":"Age-related hearing loss and the ahl locus in mice.","volume":"188","author":"Keithley","year":"2004","journal-title":"Hear. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/s0378-5955(01)00281-7","article-title":"Mitochondrial cytochrome oxidase immunolabeling in aged human temporal bones.","volume":"157","author":"Keithley","year":"2001","journal-title":"Hear. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/sj.emboj.7600951","article-title":"Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness.","volume":"25","author":"Kharkovets","year":"2006","journal-title":"EMBO J."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e0165680","DOI":"10.1371\/journal.pone.0165680","article-title":"Discovery of CDH23 as a significant contributor to progressive postlingual sensorineural hearing loss in Koreans.","volume":"11","author":"Kim","year":"2016","journal-title":"PLoS One"},{"key":"B49","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1089\/jmf.2019.4542","article-title":"Sesamum indicum L. oil and sesamin induce auditory-protective effects through changes in hearing loss-related gene expression.","volume":"23","author":"Kim","year":"2020","journal-title":"J. Med. Food"},{"key":"B50","doi-asserted-by":"publisher","first-page":"3268","DOI":"10.1121\/1.4786129","article-title":"Noise-induced and age-related hearing loss interactions.","volume":"119","author":"Kujawa","year":"2006","journal-title":"J. Acoust. Soc. Am."},{"key":"B51","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12915-022-01349-5","article-title":"Investigating the characteristics of genes and variants associated with self-reported hearing difficulty in older adults in the UK Biobank.","volume":"20","author":"Lewis","year":"2022","journal-title":"BMC Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.2741\/4445","article-title":"Transcription factors in the development of inner ear hair cells.","volume":"21","author":"Li","year":"2016","journal-title":"Front. Biosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1093\/gerona\/glr002","article-title":"Hearing loss prevalence and risk factors among older adults in the United States.","volume":"66","author":"Lin","year":"2011","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1002\/lary.21771","article-title":"The grainyhead-like 2 gene (GRHL2) single nucleotide polymorphism is not associated with age-related hearing impairment in Han Chinese.","volume":"121","author":"Lin","year":"2011","journal-title":"Laryngoscope"},{"key":"B55","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.gene.2012.01.084","article-title":"A mutation in the cdh23 gene causes age-related hearing loss in Cdh23(nmf308\/nmf308) mice.","volume":"499","author":"Liu","year":"2012","journal-title":"Gene"},{"key":"B56","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"B57","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1001\/jamaoto.2017.2513","article-title":"Association of age-related hearing loss with cognitive function, cognitive impairment, and dementia: A systematic review and meta-analysis.","volume":"144","author":"Loughrey","year":"2018","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e14305","DOI":"10.1111\/acel.14305v","article-title":"Upregulation of the Ca1.3 channel in inner hair cells by interleukin 6-dependent inflammaging contributes to age-related hearing loss.","volume":"23","author":"Lu","year":"2024","journal-title":"Aging Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1007\/s00405-015-3711-9","article-title":"The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population.","volume":"273","author":"Luo","year":"2016","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.3390\/ijms21072505","article-title":"Mitochondrial damage and necroptosis in aging cochlea.","volume":"21","author":"Lyu","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"e37753","DOI":"10.1016\/j.heliyon.2024.e37753","article-title":"Silencing of TXNIP attenuates oxidative stress injury in HEI-OC1 by inhibiting the activation of NLRP3 and NF-\u03baB.","volume":"10","author":"Ma","year":"2024","journal-title":"Heliyon"},{"key":"B62","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1001\/archotol.133.9.929","article-title":"Mitochondrial DNA haplogroups and age-related hearing loss.","volume":"133","author":"Manwaring","year":"2007","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1002\/lary.20218","article-title":"Quantification of the mitochondrial DNA common deletion in presbycusis.","volume":"119","author":"Markaryan","year":"2009","journal-title":"Laryngoscope"},{"key":"B64","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/(SICI)1096-9861(19991011)413:1<101::AID-CNE7<3.0.CO;2-L","article-title":"Cu\/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice.","volume":"413","author":"McFadden","year":"1999","journal-title":"J. Comp. Neurol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1086\/323156","article-title":"MYO6, the human homologue of the gene responsible for deafness in Snell\u2019s waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.","volume":"69","author":"Melchionda","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"B66","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s10038-022-01011-6","article-title":"Association of mitochondrial DNA haplogroup and hearing impairment with aging in Japanese general population of the Iwaki Health Promotion Project.","volume":"67","author":"Miura","year":"2022","journal-title":"J. Hum. Genet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"e40366","DOI":"10.1371\/journal.pone.0040366","article-title":"Prevalence and clinical features of hearing loss patients with CDH23 mutations: A large cohort study.","volume":"7","author":"Miyagawa","year":"2012","journal-title":"PLoS One"},{"key":"B68","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1017\/thg.2015.35","article-title":"Genetic and environmental factors in age-related hearing impairment.","volume":"18","author":"Momi","year":"2015","journal-title":"Twin Res. Hum. Genet."},{"key":"B69","first-page":"54","article-title":"Mitochondrial DNA (mtDNA) haplotypes and dysfunctions in presbyacusis.","volume":"34","author":"Mostafa","year":"2014","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"B70","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12881-017-0389-4","article-title":"Mitochondrial mutations in maternally inherited hearing loss.","volume":"18","author":"Mutai","year":"2017","journal-title":"BMC Med. Genet."},{"key":"B71","doi-asserted-by":"publisher","first-page":"15192","DOI":"10.1038\/s41598-019-51630-x","article-title":"Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment.","volume":"9","author":"Nagtegaal","year":"2019","journal-title":"Sci. Rep."},{"key":"B72","doi-asserted-by":"publisher","first-page":"108056","DOI":"10.1016\/j.isci.2023.108056ahl","article-title":"Absence of Embigin accelerates hearing loss and causes sub-viability, brain and heart defects in C57BL\/6N mice due to interaction with Cdh23.","volume":"26","author":"Newton","year":"2023","journal-title":"iScience"},{"key":"B73","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.tig.2023.12.001","article-title":"The genetic landscape of age-related hearing loss.","volume":"40","author":"Ninoyu","year":"2024","journal-title":"Trends Genet."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2077.e1","DOI":"10.1016\/j.neurobiolaging.2013.02.009","article-title":"Estrogen-related receptor gamma and hearing function: Evidence of a role in humans and mice.","volume":"34","author":"Nolan","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"B75","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3390\/genes11030273","article-title":"Clinical characteristics and in vitro analysis of MYO6 variants causing late-onset progressive hearing loss.","volume":"11","author":"Oka","year":"2020","journal-title":"Genes"},{"key":"B76","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.heares.2012.12.015","article-title":"Progressive hereditary hearing impairment caused by a MYO6 mutation resembles presbyacusis.","volume":"299","author":"Oonk","year":"2013","journal-title":"Hear. Res."},{"key":"B77","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1055\/s-0037-1601574","article-title":"HearCARE: Hearing and communication assistance for resident engagement.","volume":"38","author":"Palmer","year":"2017","journal-title":"Semin. Hear."},{"key":"B78","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s13148-024-01697-9","article-title":"A systematic review on the contribution of DNA methylation to hearing loss.","volume":"16","author":"Patil","year":"2024","journal-title":"Clin. Epigenet."},{"key":"B79","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/s41419-022-04915-5","article-title":"A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss.","volume":"13","author":"Peixoto Pinheiro","year":"2022","journal-title":"Cell Death Dis."},{"key":"B80","doi-asserted-by":"publisher","first-page":"e95413","DOI":"10.1371\/journal.pone.0095413","article-title":"Overrepresentation of glutamate signaling in Alzheimer\u2019s disease: Network-based pathway enrichment using meta-analysis of genome-wide association studies.","volume":"9","author":"P\u00e9rez-Palma","year":"2014","journal-title":"PLoS One"},{"key":"B81","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1590\/S0102-67202012000100014","article-title":"Distribution of authorship in a scientific work.","volume":"25","author":"Petroianu","year":"2012","journal-title":"Rev. Col. Bras. Cir."},{"key":"B82","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s10162-025-00994-1","article-title":"Genome-Wide association study of age-related hearing loss in CFW mice identifies multiple genes and loci, including Prkag2.","volume":"26","author":"Polesskaya","year":"2025","journal-title":"J. Assoc. Res. Otolaryngol."},{"journal-title":"Little science, big science.","year":"1965","author":"Price","key":"B83"},{"key":"B84","doi-asserted-by":"publisher","first-page":"101","DOI":"10.62347\/DTAP3592","article-title":"The emerging roles and therapeutic implications of immunosenescence-mediated inflammaging in age-related hearing loss.","volume":"13","author":"Qiu","year":"2024","journal-title":"Am. J. Stem Cells"},{"key":"B85","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.cellsig.2012.01.008","article-title":"Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling.","volume":"24","author":"Ray","year":"2012","journal-title":"Cell Signal."},{"key":"B86","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.neurobiolaging.2006.02.008","article-title":"BDNF mRNA expression and protein localization are changed in age-related hearing loss.","volume":"28","author":"R\u00fcttiger","year":"2007","journal-title":"Neurobiol. Aging"},{"key":"B87","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/s1568-1637(02)00004-1","article-title":"Molecular mechanisms of age-related hearing loss.","volume":"1","author":"Seidman","year":"2002","journal-title":"Ageing Res. Rev."},{"key":"B88","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1006\/dbio.1999.9424","article-title":"Role of myosin VI in the differentiation of cochlear hair cells.","volume":"214","author":"Self","year":"1999","journal-title":"Dev. Biol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3389\/fnins.2018.00394","article-title":"Cognitive decline, dementia, Alzheimer\u2019s disease and presbycusis: Examination of the possible molecular mechanism.","volume":"12","author":"Shen","year":"2018","journal-title":"Front. Neurosci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"3662","DOI":"10.1038\/s41598-020-60259-0","article-title":"Prevalence and clinical features of hearing loss caused by EYA4 variants.","volume":"10","author":"Shinagawa","year":"2020","journal-title":"Sci. Rep."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1369282","DOI":"10.3389\/fncel.2024.1369282","article-title":"The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing.","volume":"18","author":"Singh","year":"2024","journal-title":"Front. Cell Neurosci."},{"key":"B92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15761\/JSIN.1000168","article-title":"APOE \u03b54 allele-associated Alzheimer\u2019s disease risk is consistent with increased lifetime exposure to a neurotoxic process.","volume":"3","author":"Smith","year":"2017","journal-title":"J. Sci. Innov. Neurosci."},{"key":"B93","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.cell.2010.10.002","article-title":"Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction.","volume":"143","author":"Someya","year":"2010","journal-title":"Cell"},{"key":"B94","doi-asserted-by":"publisher","first-page":"4146","DOI":"10.3390\/ijms25084146","article-title":"Role of oxidative stress in sensorineural hearing loss.","volume":"25","author":"Teraoka","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B95","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.1093\/ndt\/gfl472","article-title":"Hearing in renal failure.","volume":"21","author":"Thodi","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"journal-title":"World Population Ageing 2019: Highlights (ST\/ESA\/SER.A\/430).","year":"2019","key":"B96"},{"key":"B97","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1007\/s00439-022-02431-2","article-title":"Variants in CDH23 cause a broad spectrum of hearing loss: From non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss.","volume":"141","author":"Usami","year":"2022","journal-title":"Hum. Genet."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1002\/humu.20375","article-title":"KCNQ4: A gene for age-related hearing impairment?","volume":"27","author":"Van Eyken","year":"2006","journal-title":"Hum. Mutat."},{"key":"B99","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/ejhg.2009.234","article-title":"A genome-wide association study for age-related hearing impairment in the Saami.","volume":"18","author":"Van Laer","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"B100","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/hmg\/ddm292","article-title":"The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment.","volume":"17","author":"Van Laer","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"B101","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1093\/ageing\/afr140","article-title":"Markers of inflammatory status are associated with hearing threshold in older people: Findings from the Hertfordshire Ageing Study.","volume":"41","author":"Verschuur","year":"2012","journal-title":"Age Ageing"},{"key":"B102","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1108\/eb026133","article-title":"Bradford\u2019s law of scattering.","volume":"4","author":"Vickery","year":"1948","journal-title":"J. Doc."},{"key":"B103","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1002\/ajmg.a.36017","article-title":"Confirmation of GRHL2 as the gene for the DFNA28 locus.","author":"Vona","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"B104","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.neuroscience.2009.01.079","article-title":"Age-related changes in glycine receptor subunit composition and binding in dorsal cochlear nucleus.","volume":"160","author":"Wang","year":"2009","journal-title":"Neuroscience"},{"key":"B105","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.arr.2015.06.002","article-title":"A review of causal mechanisms underlying the link between age-related hearing loss and cognitive decline.","volume":"23","author":"Wayne","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"B106","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1093\/hmg\/10.3.195","article-title":"Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus.","volume":"10","author":"Wayne","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"B107","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.ajhg.2019.09.008","article-title":"GWAS identifies 44 independent associated genomic loci for self-reported adult hearing difficulty in UK Biobank.","volume":"105","author":"Wells","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1002\/jnr.24549","article-title":"Genetics of age-related hearing loss.","volume":"98","author":"Wells","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"B109","doi-asserted-by":"publisher","first-page":"e35500","DOI":"10.1371\/journal.pone.0035500","article-title":"Hearing ability with age in northern European women: A new web-based approach to genetic studies.","volume":"7","author":"Wolber","year":"2012","journal-title":"PLoS One"},{"key":"B110","doi-asserted-by":"publisher","first-page":"e105729","DOI":"10.1371\/journal.pone.0105729","article-title":"Epigenome-wide DNA methylation in hearing ability: New mechanisms for an old problem.","volume":"9","author":"Wolber","year":"2014","journal-title":"PLoS One"},{"key":"B111","doi-asserted-by":"publisher","first-page":"e1008093","DOI":"10.1371\/journal.ppat.1008093","article-title":"The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation.","volume":"15","author":"Wu","year":"2019","journal-title":"PLoS Pathog."},{"key":"B112","doi-asserted-by":"publisher","first-page":"108551","DOI":"10.1016\/j.heares.2022.108551","article-title":"Age-related stereocilia pathology in the human cochlea.","volume":"422","author":"Wu","year":"2022","journal-title":"Hear. Res."},{"key":"B113","doi-asserted-by":"publisher","first-page":"21754","DOI":"10.1007\/s11356-020-12028-9","article-title":"Polymorphisms in the FAS gene are associated with susceptibility to noise-induced hearing loss.","volume":"28","author":"Xu","year":"2021","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1253574","DOI":"10.3389\/fnins.2023.1253574","article-title":"Progress on mechanisms of age-related hearing loss.","volume":"17","author":"Yang","year":"2023","journal-title":"Front. Neurosci."},{"key":"B115","doi-asserted-by":"publisher","first-page":"744","DOI":"10.3390\/genes10100744","article-title":"The prevalence and clinical characteristics of TECTA-Associated autosomal dominant hearing loss.","volume":"10","author":"Yasukawa","year":"2019","journal-title":"Genes"},{"key":"B116","doi-asserted-by":"publisher","first-page":"e88019","DOI":"10.1371\/journal.pone.0088019","article-title":"Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.","volume":"9","author":"Zeng","year":"2014","journal-title":"PLoS One"},{"key":"B117","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.heares.2019.04.012","article-title":"The TLR-4\/NF-\u03baB signaling pathway activation in cochlear inflammation of rats with noise-induced hearing loss.","volume":"379","author":"Zhang","year":"2019","journal-title":"Hear. Res."},{"key":"B118","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1097\/MAO.0000000000004098","article-title":"Caffeine ameliorates age-related hearing loss by downregulating the inflammatory pathway in mice.","volume":"45","author":"Zhang","year":"2024","journal-title":"Otol. Neurotol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1093\/hmg\/ddi010","article-title":"Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.","volume":"14","author":"Zheng","year":"2005","journal-title":"Hum. Mol. Genet."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1678115\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:24:56Z","timestamp":1762151096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1678115\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":119,"alternative-id":["10.3389\/fnagi.2025.1678115"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2025.1678115","relation":{},"ISSN":["1663-4365"],"issn-type":[{"type":"electronic","value":"1663-4365"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"article-number":"1678115"}}