{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:12:59Z","timestamp":1783649579891,"version":"3.55.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T00:00:00Z","timestamp":1735948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Province Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Gerontology"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.exger.2025.112676","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T17:34:26Z","timestamp":1736530466000},"page":"112676","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Identification of therapeutic target genes for age-related hearing loss through systematic genome-wide mendelian randomization of druggable genes"],"prefix":"10.1016","volume":"200","author":[{"given":"Kun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruru","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinbo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exger.2025.112676_bb0005","article-title":"Vasodilators and vasoactive substances for idiopathic sudden sensorineural hearing loss","volume":"4","author":"Agarwal","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.exger.2025.112676_bb0010","doi-asserted-by":"crossref","first-page":"31278","DOI":"10.1073\/pnas.2010782117","article-title":"Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis","volume":"117","author":"Boucher","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.exger.2025.112676_bb0015","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/gerona\/glaa242","article-title":"Age-related hearing loss, late-life depression, and risk for incident dementia in older adults","volume":"76","author":"Brewster","year":"2021","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"10.1016\/j.exger.2025.112676_bb0020","doi-asserted-by":"crossref","first-page":"11649","DOI":"10.1073\/pnas.0703976104","article-title":"Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins","volume":"104","author":"Brooks","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.exger.2025.112676_bb0025","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/ije\/dyv108","article-title":"Mendelian randomization: where are we now and where are we going?","volume":"44","author":"Burgess","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"10.1016\/j.exger.2025.112676_bb0030","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13708","article-title":"Cochlear Neurotrophin-3 overexpression at mid-life prevents age-related inner hair cell synaptopathy and slows age-related hearing loss","volume":"21","author":"Cassinotti","year":"2022","journal-title":"Aging Cell"},{"key":"10.1016\/j.exger.2025.112676_bb0035","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.3390\/pharmaceutics13081300","article-title":"Pulmonary delivery of curcumin and beclomethasone Dipropionate in a multicomponent Nanosuspension for the treatment of bronchial asthma","volume":"13","author":"Casula","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.exger.2025.112676_bb0040","doi-asserted-by":"crossref","first-page":"870","DOI":"10.2174\/1567205012666150710111858","article-title":"A co-module regulated by therapeutic drugs in a molecular subnetwork of Alzheimer\u2019s disease identified on the basis of traditional Chinese Medicine and SAMP8 mice","volume":"12","author":"Cheng","year":"2015","journal-title":"Curr. Alzheimer Res."},{"key":"10.1016\/j.exger.2025.112676_bb0045","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3390\/pharmaceutics13071041","article-title":"A review on recent advancement on age-related hearing loss: the applications of nanotechnology, drug pharmacology, and biotechnology","volume":"13","author":"Chester","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.exger.2025.112676_bb0050","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1038\/s41418-020-0537-9","article-title":"CD9 induces cellular senescence and aggravates atherosclerotic plaque formation","volume":"27","author":"Cho","year":"2020","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.exger.2025.112676_bb0055","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2021.745668","article-title":"Hippocampal transcriptome-wide association study reveals correlations between impaired glutamatergic synapse pathway and age-related hearing loss in BXD-recombinant inbred mice","volume":"15","author":"Deng","year":"2021","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.exger.2025.112676_bb0060","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3109\/00016489.2014.880795","article-title":"Genes involved in immunity and apoptosis are associated with human presbycusis based on microarray analysis","volume":"134","author":"Dong","year":"2014","journal-title":"Acta Otolaryngol."},{"key":"10.1016\/j.exger.2025.112676_bb0065","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aag1166","article-title":"The druggable genome and support for target identification and validation in drug development","volume":"9","author":"Finan","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.exger.2025.112676_bb0070","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.3390\/biom12111717","article-title":"Linking cerebrovascular dysfunction to age-related hearing loss and Alzheimer\u2019s disease-are systemic approaches for diagnosis and therapy required?","volume":"12","author":"F\u00f6rster","year":"2022","journal-title":"Biomolecules"},{"key":"10.1016\/j.exger.2025.112676_bb0075","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2024.176956","article-title":"Irilin D suppresses RANKL-induced osteoclastogenesis and prevents inflammation-induced bone loss by disrupting the NF-\u03baB and MAPK signaling pathways","volume":"982","author":"Gal","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.exger.2025.112676_bb0080","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S0140-6736(05)67423-5","volume":"366","author":"Gates","year":"2005","journal-title":"Presbycusis. Lancet."},{"key":"10.1016\/j.exger.2025.112676_bb0085","doi-asserted-by":"crossref","unstructured":"GBD 2019 Hearing Loss Collaborators. Hearing loss prevalence and years lived with disability, 1990\u20132019: findings from the Global Burden of Disease Study 2019. Lancet. 2021; 397: 996\u20131009. doi:https:\/\/doi.org\/10.1016\/S0140-6736(21)00516-X.","DOI":"10.1016\/S0140-6736(21)00516-X"},{"key":"10.1016\/j.exger.2025.112676_bb0090","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1038\/cdd.2015.15","article-title":"Bak apoptotic pores involve a flexible C-terminal region and juxtaposition of the C-terminal transmembrane domains","volume":"22","author":"Iyer","year":"2015","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.exger.2025.112676_bb0095","doi-asserted-by":"crossref","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":"10.1016\/j.exger.2025.112676_bb0100","first-page":"1449","article-title":"CD9 expression in vascular aging and atherosclerosis","volume":"35","author":"Kim","year":"2020","journal-title":"Histol. Histopathol."},{"key":"10.1016\/j.exger.2025.112676_bb0105","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.17981","article-title":"Comprehensive analysis of macrophage-associated inflammatory genes in AMI based on bulk combined with single-cell sequencing data","volume":"12","author":"Kong","year":"2024","journal-title":"PeerJ"},{"key":"10.1016\/j.exger.2025.112676_bb0110","doi-asserted-by":"crossref","unstructured":"Lai YJ, Zhu BL, Sun F, Luo D, Ma YL, Luo B, Tang J, Xiong MJ, Liu L, Long Y, Hu XT, He L, Deng XJ, Zhang JH, Yang J, Yan Z, Chen GJ. Estrogen receptor \u03b1 promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP\/PS1 mice. Aging Cell 2019 Aug; 18(4): e12961. doi:https:\/\/doi.org\/10.1111\/acel.12961. (Epub 2019 Apr 22. PMID: 31012223; PMCID: PMC6612642).","DOI":"10.1111\/acel.12961"},{"key":"10.1016\/j.exger.2025.112676_bb0115","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/NEN.0b013e3182417387","article-title":"Alteration of the cerebral zinc pool in a mouse model of Alzheimer disease","volume":"71","author":"Lee","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.exger.2025.112676_bb0120","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/biof.1400","article-title":"Effect of resveratrol and pterostilbene on aging and longevity","volume":"44","author":"Li","year":"2018","journal-title":"Biofactors"},{"key":"10.1016\/j.exger.2025.112676_bb0125","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1056\/NEJMcp2306778","article-title":"Age-related hearing loss","volume":"390","author":"Lin","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.exger.2025.112676_bb0130","doi-asserted-by":"crossref","first-page":"12788","DOI":"10.1021\/acs.jafc.9b07860","article-title":"Occurrence, bioavailability, anti-inflammatory, and anticancer effects of Pterostilbene","volume":"68","author":"Lin","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.exger.2025.112676_bb0135","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.3390\/molecules27144655","article-title":"Mechanistic insights into the mechanism of inhibitor selectivity toward the dark kinase STK17B against its high homology STK17A","volume":"27","author":"Liu","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.exger.2025.112676_bb0140","first-page":"24","article-title":"Acquired sensorineural hearing loss, oxidative stress, and microRNAs","author":"Nunez","year":"2024","journal-title":"Neural Regen. Res."},{"key":"10.1016\/j.exger.2025.112676_bb0145","doi-asserted-by":"crossref","unstructured":"Storm CS, Kia DA, Almramhi MM, Bandres-Ciga S, Finan C; International Parkinson's Disease Genomics Consortium (IPDGC); Hingorani AD, Wood NW. Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome. Nat. Commun.. 2021 20; 12: 7342. doi:https:\/\/doi.org\/10.1038\/s41467-021-26280-1.","DOI":"10.1038\/s41467-021-26280-1"},{"key":"10.1016\/j.exger.2025.112676_bb0150","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.3324\/haematol.2022.282612","article-title":"Momelotinib (JAK1\/JAK2\/ACVR1 inhibitor): mechanism of action, clinical trial reports, and therapeutic prospects beyond myelofibrosis","volume":"108","author":"Tefferi","year":"2023","journal-title":"Haematologica"},{"key":"10.1016\/j.exger.2025.112676_bb0155","first-page":"S1","article-title":"Clinical practice guideline: age-related hearing loss","volume":"2","author":"Tsai Do","year":"2024","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"10.1016\/j.exger.2025.112676_bb0160","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.heares.2015.04.014","article-title":"Cochlear neuropathy in human presbycusis: confocal analysis of hidden hearing loss in post-mortem tissue","volume":"327","author":"Viana","year":"2015","journal-title":"Hear. Res."},{"key":"10.1016\/j.exger.2025.112676_bb0165","article-title":"Steroids for idiopathic sudden sensorineural hearing loss","volume":"7","author":"Wei","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.exger.2025.112676_bb0170","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0140-6736(21)00522-5","article-title":"Addressing the global burden of hearing loss","volume":"397","author":"Wilson","year":"2021","journal-title":"Lancet"},{"key":"10.1016\/j.exger.2025.112676_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.heares.2024.109148","article-title":"The therapeutic effect and underlying biochemical mechanism of methylprednisolone and D-methionine in \u201crescuing\u201d noise-induced hearing loss in guinea pigs","volume":"454","author":"Wu","year":"2024","journal-title":"Hear. Res."},{"key":"10.1016\/j.exger.2025.112676_bb0180","doi-asserted-by":"crossref","first-page":"6673","DOI":"10.1111\/ejn.15465","article-title":"Serine\/threonine kinase 17b (STK17B) signalling regulates Purkinje cell dendritic development and is altered in multiple spinocerebellar ataxias","volume":"54","author":"Wu","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.exger.2025.112676_bb0185","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.770329","article-title":"Neuroprotective and anti-inflammatory effect of Pterostilbene against cerebral ischemia\/reperfusion injury via suppression of COX-2","volume":"12","author":"Yan","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.exger.2025.112676_bb0190","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.bbr.2012.01.043","article-title":"Autocrine motility factor receptor is involved in the process of learning and memory in the central nervous system","volume":"229","author":"Yang","year":"2012","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.exger.2025.112676_bb0195","first-page":"30","article-title":"Identification of potential causal genes for neurodegenerative diseases by mitochondria-related genome-wide Mendelian randomization","author":"Yin","year":"2024","journal-title":"Mol. Neurobiol."},{"issue":"1","key":"10.1016\/j.exger.2025.112676_bb0200","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s10194-024-01805-3","article-title":"Identifying therapeutic target genes for migraine by systematic druggable genome-wide Mendelian randomization","volume":"25","author":"Zhang","year":"2024","journal-title":"J. Headache Pain"},{"key":"10.1016\/j.exger.2025.112676_bb0205","doi-asserted-by":"crossref","DOI":"10.1016\/j.mad.2024.111964","article-title":"Sestrin2 plays a protective role in age-related hearing loss by inhibiting NLRP3-inflammasome activity","volume":"221","author":"Zheng","year":"2024","journal-title":"Mech. Ageing Dev."},{"key":"10.1016\/j.exger.2025.112676_bb0210","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2024.1428564","article-title":"Age-related hearing loss in older adults: etiology and rehabilitation strategies","volume":"18","author":"Zheng","year":"2024","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.exger.2025.112676_bb0215","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/WCO.0b013e3283484b87","article-title":"Genetics of Parkinson\u2019s disease and essential tremor","volume":"24","author":"Zimprich","year":"2011","journal-title":"Curr. Opin. Neurol."}],"container-title":["Experimental Gerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S053155652500004X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S053155652500004X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T22:13:32Z","timestamp":1744236812000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S053155652500004X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":43,"alternative-id":["S053155652500004X"],"URL":"https:\/\/doi.org\/10.1016\/j.exger.2025.112676","relation":{},"ISSN":["0531-5565"],"issn-type":[{"value":"0531-5565","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of therapeutic target genes for age-related hearing loss through systematic genome-wide mendelian randomization of druggable genes","name":"articletitle","label":"Article Title"},{"value":"Experimental Gerontology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exger.2025.112676","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112676"}}