{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:24:49Z","timestamp":1772454289426,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Chongqing Science and Health Union","award":["No2022DBXM006"],"award-info":[{"award-number":["No2022DBXM006"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81873702"],"award-info":[{"award-number":["No. 81873702"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"crossref","award":["No.2022NSCQ-MSX2839"],"award-info":[{"award-number":["No.2022NSCQ-MSX2839"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"crossref","award":["Nos. CSTB2022NSCQ-MSX0553"],"award-info":[{"award-number":["Nos. CSTB2022NSCQ-MSX0553"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"crossref","award":["2023jsqd180"],"award-info":[{"award-number":["2023jsqd180"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biogerontology"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1007\/s10522-025-10261-8","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T20:00:14Z","timestamp":1748980814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identifying a gene signature for age-related hearing loss through machine learning and revealing the effect of the CTSS on the mice cochlea"],"prefix":"10.1007","volume":"26","author":[{"given":"Xu","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menglong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailan","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"10261_CR1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3390\/pathophysiology31030035","volume":"31","author":"TA Ajani","year":"2024","unstructured":"Ajani TA, Magwebu ZE, Chauke CG, Obikeze K (2024) Advances in cathepsin s inhibition: challenges and breakthroughs in drug development. Pathophysiology 31:471\u2013487","journal-title":"Pathophysiology"},{"key":"10261_CR2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25\u20139","journal-title":"Nat Genet"},{"key":"10261_CR3","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.3390\/cells10102761","volume":"10","author":"P Bazard","year":"2021","unstructured":"Bazard P, Pineros J, Frisina RD, Bauer MA, Acosta AA, Paganella LR, Borakiewicz D, Thivierge M, Mannering FL, Zhu X, Ding B (2021) Cochlear inflammaging in relation to ion channels and mitochondrial functions. Cells 10:2761","journal-title":"Cells"},{"key":"10261_CR4","doi-asserted-by":"publisher","first-page":"242","DOI":"10.2471\/BLT.21.285643","volume":"99","author":"S Chadha","year":"2021","unstructured":"Chadha S, Kamenov K, Cieza A (2021) The world report on hearing, 2021. Bull World Health Organ 99:242-242A","journal-title":"Bull World Health Organ"},{"key":"10261_CR5","doi-asserted-by":"publisher","first-page":"6667531","DOI":"10.1155\/2021\/6667531","volume":"2021","author":"Z Chen","year":"2021","unstructured":"Chen Z, Zhang Y, Zhang J, Zhou R, Zhong Z, Wei C, Chen J, Liu Y (2021) Cochlear synaptopathy: a primary factor affecting speech recognition performance in presbycusis. Biomed Res Int 2021:6667531","journal-title":"Biomed Res Int"},{"key":"10261_CR6","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1161\/CIRCULATIONAHA.115.001593","volume":"132","author":"RC Deo","year":"2015","unstructured":"Deo RC (2015) Machine learning in medicine. Circulation 132:1920\u20131930","journal-title":"Circulation"},{"key":"10261_CR7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.jneumeth.2008.02.022","volume":"171","author":"M D'Souza","year":"2008","unstructured":"D\u2019Souza M, Zhu X, Frisina RD (2008) Novel approach to select genes from RMA normalized microarray data using functional hearing tests in aging mice. J Neurosci Methods 171:279\u2013287","journal-title":"J Neurosci Methods"},{"key":"10261_CR8","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1016\/j.ajpath.2014.11.026","volume":"185","author":"JL Figueiredo","year":"2015","unstructured":"Figueiredo JL, Aikawa M, Zheng C, Aaron J, Lax L, Libby P, de Lima Filho JL, Gruener S, Fingerle J, Haap W, Hartmann G, Aikawa E (2015) Selective cathepsin S inhibition attenuates atherosclerosis in apolipoprotein E-deficient mice with chronic renal disease. Am J Pathol 185:1156\u20131166","journal-title":"Am J Pathol"},{"key":"10261_CR9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1167\/iovs.64.11.7","volume":"64","author":"JG Galletti","year":"2023","unstructured":"Galletti JG, Scholand KK, Trujillo-Vargas CM, Haap W, Santos-Ferreira T, Ullmer C, Yu Z, de Paiva CS (2023) Effects of cathepsin S inhibition in the age-related dry eye phenotype. Invest Ophthalmol Vis Sci 64:7","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10261_CR10","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.neuron.2020.08.003","volume":"108","author":"TD Griffiths","year":"2020","unstructured":"Griffiths TD, Lad M, Kumar S, Holmes E, Mcmurray B, Maguire EA, Billig AJ, Sedley W (2020) How can hearing loss cause dementia? Neuron 108:401\u2013412","journal-title":"Neuron"},{"key":"10261_CR11","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1182\/blood.V81.6.1607.1607","volume":"81","author":"CL Holness","year":"1993","unstructured":"Holness CL, Simmons DL (1993) Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81:1607\u20131613","journal-title":"Blood"},{"key":"10261_CR12","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1293\/tox.2017-0031","volume":"30","author":"Y Horai","year":"2017","unstructured":"Horai Y, Kakimoto T, Takemoto K, Tanaka M (2017) Quantitative analysis of histopathological findings using image processing software. J Toxicol Pathol 30:351\u2013358","journal-title":"J Toxicol Pathol"},{"key":"10261_CR13","doi-asserted-by":"publisher","first-page":"9","DOI":"10.5603\/FHC.a2020.0001","volume":"58","author":"WX Hu","year":"2020","unstructured":"Hu WX, Li H, Jiang JZ (2020) MiR-491-3p is down-regulated in postmenopausal osteoporosis and affects growth, differentiation and apoptosis of hFOB1.19 cells through targeting CTSS. Folia Histochem Cytobiol 58:9\u201316","journal-title":"Folia Histochem Cytobiol"},{"key":"10261_CR14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27\u201330","journal-title":"Nucleic Acids Res"},{"key":"10261_CR15","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinform 9:559","journal-title":"BMC Bioinform"},{"key":"10261_CR16","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1517\/13543776.2011.553800","volume":"21","author":"A Lee-Dutra","year":"2011","unstructured":"Lee-Dutra A, Wiener DK, Sun S (2011) Cathepsin S inhibitors: 2004\u20132010. Expert Opin Ther Pat 21:311\u2013337","journal-title":"Expert Opin Ther Pat"},{"key":"10261_CR17","doi-asserted-by":"publisher","first-page":"757","DOI":"10.2147\/CIA.S158513","volume":"13","author":"I Liguori","year":"2018","unstructured":"Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757\u2013772","journal-title":"Clin Interv Aging"},{"key":"10261_CR18","doi-asserted-by":"publisher","first-page":"1339134","DOI":"10.3389\/fnins.2023.1339134","volume":"17","author":"YC Liu","year":"2023","unstructured":"Liu YC, Xu K (2023) Macrophage-related immune responses in inner ear: a potential therapeutic target for sensorineural hearing loss. Front Neurosci 17:1339134","journal-title":"Front Neurosci"},{"key":"10261_CR19","doi-asserted-by":"publisher","first-page":"108859","DOI":"10.1016\/j.heares.2023.108859","volume":"438","author":"X Luo","year":"2023","unstructured":"Luo X, Hu Y, Zhou X, Zhang C, Feng M, Yang T, Yuan W (2023) Potential roles for lncRNA Mirg\/Foxp1 in an ARHL model created using C57BL\/6J mice. Hear Res 438:108859","journal-title":"Hear Res"},{"key":"10261_CR20","doi-asserted-by":"publisher","first-page":"140465","DOI":"10.1016\/j.bbapap.2020.140465","volume":"1868","author":"H Nakanishi","year":"2020","unstructured":"Nakanishi H (2020) Cathepsin regulation on microglial function. Biochim Biophys Acta Proteins Proteom 1868:140465","journal-title":"Biochim Biophys Acta Proteins Proteom"},{"key":"10261_CR21","doi-asserted-by":"publisher","first-page":"895","DOI":"10.3389\/fneur.2019.00895","volume":"10","author":"KV Noble","year":"2019","unstructured":"Noble KV, Liu T, Matthews LJ, Schulte BA, Lang H (2019) Age-related changes in immune cells of the human cochlea. Front Neurol 10:895","journal-title":"Front Neurol"},{"key":"10261_CR22","doi-asserted-by":"publisher","first-page":"680856","DOI":"10.3389\/fnins.2021.680856","volume":"15","author":"V Paplou","year":"2021","unstructured":"Paplou V, Schubert NMA, Pyott SJ (2021) Age-related changes in the cochlea and vestibule: shared patterns and processes. Front Neurosci 15:680856","journal-title":"Front Neurosci"},{"key":"10261_CR23","doi-asserted-by":"publisher","first-page":"1308823","DOI":"10.3389\/fneur.2023.1308823","volume":"14","author":"S Parekh","year":"2023","unstructured":"Parekh S, Kaur T (2023) Cochlear inflammaging: cellular and molecular players of the innate and adaptive immune system in age-related hearing loss. Front Neurol 14:1308823","journal-title":"Front Neurol"},{"key":"10261_CR24","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1176\/appi.ajp.2017.17040423","volume":"175","author":"BR Rutherford","year":"2018","unstructured":"Rutherford BR, Brewster K, Golub JS, Kim AH, Roose SP (2018) Sensation and psychiatry: linking age-related hearing loss to late-life depression and cognitive decline. Am J Psychiatry 175:215\u2013224","journal-title":"Am J Psychiatry"},{"key":"10261_CR25","doi-asserted-by":"publisher","first-page":"846804","DOI":"10.3389\/fnagi.2022.846804","volume":"14","author":"BJ Seicol","year":"2022","unstructured":"Seicol BJ, Lin S, Xie R (2022) Age-related hearing loss is accompanied by chronic inflammation in the cochlea and the cochlear nucleus. Front Aging Neurosci 14:846804","journal-title":"Front Aging Neurosci"},{"key":"10261_CR26","first-page":"5611","volume":"9","author":"X Shi","year":"2017","unstructured":"Shi X, Qiu S, Zhuang W, Yuan N, Wang C, Zhang S, Sun T, Guo W, Gao F, Yang S, Qiao Y (2017) NLRP3-inflammasomes are triggered by age-related hearing loss in the inner ear of mice. Am J Transl Res 9:5611\u20135618","journal-title":"Am J Transl Res"},{"key":"10261_CR27","doi-asserted-by":"publisher","first-page":"101106","DOI":"10.1016\/j.mam.2022.101106","volume":"88","author":"P Smyth","year":"2022","unstructured":"Smyth P, Sasiwachirangkul J, Williams R, Scott CJ (2022) Cathepsin S (CTSS) activity in health and disease\u2014a treasure trove of untapped clinical potential. Mol Aspects Med 88:101106","journal-title":"Mol Aspects Med"},{"key":"10261_CR28","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.brainres.2007.08.090","volume":"1182","author":"S Someya","year":"2007","unstructured":"Someya S, Yamasoba T, Prolla TA, Tanokura M (2007) Genes encoding mitochondrial respiratory chain components are profoundly down-regulated with aging in the cochlea of DBA\/2J mice. Brain Res 1182:26\u201333","journal-title":"Brain Res"},{"key":"10261_CR29","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1172\/JCI181","volume":"102","author":"GK Sukhova","year":"1998","unstructured":"Sukhova GK, Shi GP, Simon DI, Chapman HA, Libby P (1998) Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest 102:576\u2013583","journal-title":"J Clin Invest"},{"key":"10261_CR30","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.neurobiolaging.2006.05.021","volume":"28","author":"SF Tadros","year":"2007","unstructured":"Tadros SF, D\u2019Souza M, Zettel ML, Zhu X, Lynch-Erhardt M, Frisina RD (2007) Serotonin 2B receptor: upregulated with age and hearing loss in mouse auditory system. Neurobiol Aging 28:1112\u201323","journal-title":"Neurobiol Aging"},{"key":"10261_CR31","first-page":"136","volume":"3","author":"WY Wang","year":"2015","unstructured":"Wang WY, Tan MS, Yu JT, Tan L (2015) Role of pro-inflammatory cytokines released from microglia in Alzheimer\u2019s disease. Ann Transl Med 3:136","journal-title":"Ann Transl Med"},{"key":"10261_CR32","doi-asserted-by":"publisher","first-page":"111","DOI":"10.5551\/jat.RV17016","volume":"25","author":"H Wu","year":"2018","unstructured":"Wu H, Du Q, Dai Q, Ge J, Cheng X (2018) Cysteine protease cathepsins in atherosclerotic cardiovascular diseases. J Atheroscler Thromb 25:111\u2013123","journal-title":"J Atheroscler Thromb"},{"key":"10261_CR33","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fncel.2015.00276","volume":"9","author":"CH Yang","year":"2015","unstructured":"Yang CH, Schrepfer T, Schacht J (2015) Age-related hearing impairment and the triad of acquired hearing loss. Front Cell Neurosci 9:276","journal-title":"Front Cell Neurosci"},{"key":"10261_CR34","doi-asserted-by":"publisher","first-page":"1276963","DOI":"10.3389\/fgene.2023.1276963","volume":"14","author":"Y Yin","year":"2023","unstructured":"Yin Y, Chen C, Zhang D, Han Q, Wang Z, Huang Z, Chen H, Sun L, Fei S, Tao J, Han Z, Tan R, Gu M, Ju X (2023) Construction of predictive model of interstitial fibrosis and tubular atrophy after kidney transplantation with machine learning algorithms. Front Genet 14:1276963","journal-title":"Front Genet"},{"key":"10261_CR35","doi-asserted-by":"publisher","first-page":"1290036","DOI":"10.3389\/fgene.2023.1290036","volume":"14","author":"H Zhang","year":"2023","unstructured":"Zhang H, Zhang H, Yang H, Shuid AN, Sandai D, Chen X (2023) Machine learning-based integrated identification of predictive combined diagnostic biomarkers for endometriosis. Front Genet 14:1290036","journal-title":"Front Genet"}],"container-title":["Biogerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-025-10261-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10522-025-10261-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-025-10261-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:24:57Z","timestamp":1750915497000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10522-025-10261-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10261"],"URL":"https:\/\/doi.org\/10.1007\/s10522-025-10261-8","relation":{},"ISSN":["1389-5729","1573-6768"],"issn-type":[{"value":"1389-5729","type":"print"},{"value":"1573-6768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"10 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The animal study protocol was approved by the Ethics Committee of Chongqing General Hospital (KY S2022-019-01; data of approval: 31 May 2022). The animal study protocol was approved by the Ethics Committee of Chongqing General Hospital (KY S2022-019-01; data of approval: 31 May 2022). All animal experiments should comply with ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"119"}}