{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:39:52Z","timestamp":1792143592591,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG067988"],"award-info":[{"award-number":["P30AG067988"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["100499"],"award-info":[{"award-number":["100499"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["205585"],"award-info":[{"award-number":["205585"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["118555"],"award-info":[{"award-number":["118555"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["141054"],"award-info":[{"award-number":["141054"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["264146"],"award-info":[{"award-number":["264146"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["308248"],"award-info":[{"award-number":["308248"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["307339"],"award-info":[{"award-number":["307339"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["328685"],"award-info":[{"award-number":["328685"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023699","name":"Health Data Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018517","name":"Office for National Statistics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018517","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ\u2010specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ\u2010specific levels\u2014including the brain\u2014in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain\u2010specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, related dementia, and mortality among individuals with MDD in the UK Biobank. Evidence of depressive episode remission attenuated the association between MDD and systemic and brain\u2010specific proteomic aging acceleration. Finally, Mendelian randomization analyses revealed a causal effect of MDD on systemic and brain\u2010specific proteomic aging acceleration. Our results suggest a strong bidirectional association between MDD and biological aging acceleration. Biological aging acceleration, assessed by proteomic systemic and organ\u2010specific clocks, can serve as a novel therapeutic target for treating MDD and for mitigating the long\u2010term risks of adverse health outcomes associated with this condition.<\/jats:p>","DOI":"10.1111\/acel.70310","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T09:45:08Z","timestamp":1764841508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Biological Aging Acceleration in Major Depressive Disorder: A Multi\u2010Omics Analysis"],"prefix":"10.1111","volume":"25","author":[{"given":"Breno Satler","family":"Diniz","sequence":"first","affiliation":[{"name":"UConn Center on Aging University of Connecticut Health Center  Farmington Connecticut USA"},{"name":"Department of Psychiatry University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangshu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-8483","authenticated-orcid":false,"given":"Gabin","family":"Drouard","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eero","family":"Vuoksimaa","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miina","family":"Ollikainen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Lenze","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University in St Louis  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota  St Paul Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Fortinsky","sequence":"additional","affiliation":[{"name":"UConn Center on Aging University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8387-7040","authenticated-orcid":false,"given":"George A.","family":"Kuchel","sequence":"additional","affiliation":[{"name":"UConn Center on Aging University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Kaprio","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Ling","family":"Kuo","sequence":"additional","affiliation":[{"name":"UConn Center on Aging University of Connecticut Health Center  Farmington Connecticut USA"},{"name":"Department of Public Health Sciences University of Connecticut Health Center  Farmington Connecticut USA"},{"name":"The Cato T. Laurencin Institute for Regenerative Engineering University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010016\u20100720\u20105"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.22f14733"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2024.07.005"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.112.118307"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44220\u2010025\u201000460\u20100"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010019\u20100541\u20103"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010021\u201000368\u20101"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.24.24306270"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0231627"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.118.312816"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f2570"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010023\u201002670\u20105"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201038013\u20107"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjo.2020.145"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.10.005"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17060595"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888\u2010018\u20101657\u20103"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.4602"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.120.14973"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2019.54"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2016.0004"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12265\u2010020\u201009985\u20104"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.10"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14195"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2414086122"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e31826ddbed"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101805"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.12.002"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty476"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13325"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.inpsyc.2025.100113"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010024\u201001046\u20103"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2018.20.1\/bpenninx"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010021\u201001302\u20100"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.33448"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010023\u201001594\u20107"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105581"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44220\u2010023\u201000033\u2010z"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010024\u201001016\u2010z"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7378.1437"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2017.03.005"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2021.07.082"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006592\u20106"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2023.115103"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glad082"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.2502"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(13)61611\u20106"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2024.4305"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2022.08.026"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:56:29Z","timestamp":1774353389000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/acel.70310"],"URL":"https:\/\/doi.org\/10.1111\/acel.70310","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]},"assertion":[{"value":"2025-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70310"}}