{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:16:54Z","timestamp":1790471814535,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T00:00:00Z","timestamp":1606003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007136","name":"Secretar\u00eda de Estado de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["MINECO\/FEDER SAF2017\u201086107\u2010R"],"award-info":[{"award-number":["MINECO\/FEDER SAF2017\u201086107\u2010R"]}],"id":[{"id":"10.13039\/501100007136","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["FEDER\/CM\u2010B2017\/BMD\u20103688"],"award-info":[{"award-number":["FEDER\/CM\u2010B2017\/BMD\u20103688"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u20106\u2010phosphate dehydrogenase (G6PD), which catalyzes the rate\u2010limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (<jats:italic>G6PD<\/jats:italic>\u2010Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild\u2010type 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\u2010month\u2010old <jats:italic>G6PD<\/jats:italic>\u2010Tg mice than in wild\u2010type counterparts, whereas the levels of pro\u2010apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL<jats:sup>+<\/jats:sup> apoptotic cells were all lower in 9\u2010month\u2010old <jats:italic>G6PD<\/jats:italic>\u2010Tg than in wild\u2010type counterparts. Unexpectedly, <jats:italic>G6PD<\/jats:italic> overexpression triggered low\u2010grade 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.<\/jats:p>","DOI":"10.1111\/acel.13275","type":"journal-article","created":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T17:26:42Z","timestamp":1606066002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["<i>G6PD<\/i> overexpression protects from oxidative stress and age\u2010related hearing loss"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-9285","authenticated-orcid":false,"given":"Jose M.","family":"Berm\u00fadez\u2010Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Institute for Biomedical Research \u201cAlberto Sols\u201d (IIBM) Spanish National Research Council\u2010Autonomous University of Madrid (CSIC\u2010UAM Madrid Spain"},{"name":"Rare Diseases Networking Biomedical Research Centre (CIBERER) CIBER Carlos III Institute of Health Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0757-6163","authenticated-orcid":false,"given":"Adelaida M.","family":"Celaya","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research \u201cAlberto Sols\u201d (IIBM) Spanish National Research Council\u2010Autonomous University of Madrid (CSIC\u2010UAM Madrid Spain"},{"name":"Rare Diseases Networking Biomedical Research Centre (CIBERER) CIBER Carlos III Institute of Health Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hijazo\u2010Pechero","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research \u201cAlberto Sols\u201d (IIBM) Spanish National Research Council\u2010Autonomous University of Madrid (CSIC\u2010UAM Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-719X","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"INSERM \u2010 UMR 1051 Institut des Neurosciences de Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7177-9312","authenticated-orcid":false,"given":"Manuel","family":"Serrano","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-0500","authenticated-orcid":false,"given":"Isabel","family":"Varela\u2010Nieto","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research \u201cAlberto Sols\u201d (IIBM) Spanish National Research Council\u2010Autonomous University of Madrid (CSIC\u2010UAM Madrid Spain"},{"name":"Rare Diseases Networking Biomedical Research Centre (CIBERER) CIBER Carlos III Institute of Health Madrid Spain"},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010019\u20101493\u20106"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2005.04584.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.39159"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13080"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401420"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010014\u20100934\u20102"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(05)67423\u20105"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01260\u201012"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4599"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.06.025"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.041"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2011.11.007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2003.11.020"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13016"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2004.05.022"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.05.008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4923\u201013.2014"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201055329\u2010x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2017.0930"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14\u2010259283"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0197\u20104580(99)00018\u20104"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-13473-4"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4533"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10894"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.3.485"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s101620010043"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00205.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00107"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.554"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.5.2750"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008699"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2009.04.019"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(01)00224-6"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908786106"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1017"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2017.09.001"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7342"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00053.2017"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2017.10.002"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0519\u201017.2017"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201023436\u2010w"},{"key":"e_1_2_9_45_1","volume-title":"Deafness and hearing loss","author":"WHO","year":"2018"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(00)80611\u2010X"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09\u2010135731"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.132"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076\u20106879(05)01028\u20101"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13275","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13275","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T20:16:38Z","timestamp":1729714598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,22]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/acel.13275"],"URL":"https:\/\/doi.org\/10.1111\/acel.13275","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,22]]},"assertion":[{"value":"2020-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13275"}}