{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:26:52Z","timestamp":1791847612454,"version":"4.3.4"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,11,17]]},"abstract":"<jats:p>\n                    Age-related hearing loss (AHL), known as presbycusis, is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. The molecular mechanisms underlying AHL are unknown, and currently there is no treatment for the disorder. Here we report that C57BL\/6J mice with a deletion of the mitochondrial pro-apoptotic gene\n                    <jats:italic>Bak<\/jats:italic>\n                    exhibit reduced age-related apoptotic cell death of spiral ganglion neurons and hair cells in the cochlea, and prevention of AHL. Oxidative stress induces\n                    <jats:italic>Bak<\/jats:italic>\n                    expression in primary cochlear cells, and Bak deficiency prevents apoptotic cell death. Furthermore, a mitochondrially targeted catalase transgene suppresses\n                    <jats:italic>Bak<\/jats:italic>\n                    expression in the cochlea, reduces cochlear cell death, and prevents AHL. Oral supplementation with the mitochondrial antioxidants \u03b1-lipoic acid and coenzyme Q\n                    <jats:sub>10<\/jats:sub>\n                    also suppresses\n                    <jats:italic>Bak<\/jats:italic>\n                    expression in the cochlea, reduces cochlear cell death, and prevents AHL. Thus, induction of a Bak-dependent mitochondrial apoptosis program in response to oxidative stress is a key mechanism of AHL in C57BL\/6J mice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0908786106","type":"journal-article","created":{"date-parts":[[2009,11,9]],"date-time":"2009-11-09T22:20:09Z","timestamp":1257805209000},"page":"19432-19437","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":310,"title":["Age-related hearing loss in C57BL\/6J mice is mediated by Bak-dependent mitochondrial apoptosis"],"prefix":"10.1073","volume":"106","author":[{"given":"Shinichi","family":"Someya","sequence":"first","affiliation":[{"name":"Departments of aGenetics and Medical Genetics and"},{"name":"Departments of bApplied Biological Chemistry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinze","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Aging and Geriatrics, University of Florida, Gainesville, FL 32611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kondo","sequence":"additional","affiliation":[{"name":"Otolaryngology and Head and Neck Surgery, University of Tokyo, Tokyo 113-8657, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalian","family":"Ding","sequence":"additional","affiliation":[{"name":"Center for Hearing and Deafness, University at Buffalo, Buffalo, NY 14214; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Salvi","sequence":"additional","affiliation":[{"name":"Center for Hearing and Deafness, University at Buffalo, Buffalo, NY 14214; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Yamasoba","sequence":"additional","affiliation":[{"name":"Otolaryngology and Head and Neck Surgery, University of Tokyo, Tokyo 113-8657, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Weindruch","sequence":"additional","affiliation":[{"name":"Medicine and Veterans Administration Hospital, Geriatric Research Education and Clinical Center, University of Wisconsin, Madison, WI 53706;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan","family":"Leeuwenburgh","sequence":"additional","affiliation":[{"name":"Department of Aging and Geriatrics, University of Florida, Gainesville, FL 32611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Tanokura","sequence":"additional","affiliation":[{"name":"Departments of bApplied Biological Chemistry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas A.","family":"Prolla","sequence":"additional","affiliation":[{"name":"Departments of aGenetics and Medical Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,11,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67423-5"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2006.06.004"},{"key":"e_1_3_3_3_2","unstructured":"Aging statistics Available at http:\/\/www.aoa.gov\/AoARoot\/Aging_Statistics\/index.aspx. (2009)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00003-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(03)00365-4"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.06.024"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(87)90137-7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.03.017"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1226"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509776102"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.39.110304.095751"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.AUD.0000079802.82344.B5"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2008.05.002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2000.570601.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(97)00077-4"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112125"},{"key":"e_1_3_3_17_2","unstructured":"R Weindruch RL Walford The retardation of aging and disease by dietary restriction.  (Charles C Thomas Springfield 1988)."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2308"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.01.014"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2003.10.003"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099196"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00136-2"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80385-2"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhn167"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708451200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000081284"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106653"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9355-4"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1054\/mehy.2000.1194"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.12.040"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2007.03.006"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01202-X"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01361-9"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.03.149"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.15.6728-6741.2004"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00050-9"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1123"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6377"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2008.06.001"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.06.025"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-008-0266-x"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.3109\/00206098809081601"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199710023371407"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200005000-00003"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703976104"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.10.045"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.08.090"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2006.07.015"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2006.014"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002865"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01983-6"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0908786106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:44:35Z","timestamp":1649789075000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0908786106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,17]]},"references-count":51,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2009,11,17]]}},"alternative-id":["10.1073\/pnas.0908786106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0908786106","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1439957.918055","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,17]]},"assertion":[{"value":"2009-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}