{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:51:05Z","timestamp":1784922665433,"version":"3.55.0"},"reference-count":88,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2021SGR782"],"award-info":[{"award-number":["2021SGR782"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The onset of multiple sclerosis (MS) in older individuals correlates with a higher risk of developing primary progressive MS, faster progression to secondary progressive MS, and increased disability accumulation. This phenomenon can be related to age\u2010related changes in the immune system: with age, the immune system undergoes a process called immunosenescence, characterized by a decline in the function of both the innate and adaptive immune responses. This decline can lead to a decreased ability to control inflammation and repair damaged tissue. Additionally, older individuals often experience a shift toward a more pro\u2010inflammatory state, known as inflammaging, which can exacerbate the progression of neurodegenerative diseases like MS. Therefore, age\u2010related alterations in the immune system could be responsible for the difference in the phenotype of MS observed in older and younger patients. In this study, we investigated the effects of age on the immunopathogenesis of experimental autoimmune encephalomyelitis (EAE). Our findings indicate that EAE is more severe in aged mice due to a more inflammatory and neurodegenerative environment in the central nervous system. Age\u2010related changes predominantly affect adaptive immunity, characterized by altered T cell ratios, a pro\u2010inflammatory Th1 response, increased regulatory T cells, exhaustion of T cells, altered B cell antigen presentation, and reduced NK cell maturation and cytotoxicity. Transcriptomic analysis reveals that fewer pathways and transcription factors are activated with age in EAE. These findings allow us to identify potential therapeutic targets specific to elderly MS patients and work on their development in the future.<\/jats:p>","DOI":"10.1111\/acel.14491","type":"journal-article","created":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T23:04:02Z","timestamp":1738537442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis: Role of Immunosenescence"],"prefix":"10.1111","volume":"24","author":[{"given":"Mar\u00eda","family":"Dema","sequence":"first","affiliation":[{"name":"Servei de Neurologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herena","family":"Eixarch","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnau","family":"Hervera","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Castillo","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa M.","family":"Villar","sequence":"additional","affiliation":[{"name":"Departmento de Inmunolog\u00eda Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Montalban","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9949-5901","authenticated-orcid":false,"given":"Carmen","family":"Espejo","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2022.104580"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201038238\u20106"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.2.7348"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.08.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2024.100237"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI156254"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.158153"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.11.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15751"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2013.11.007"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3704"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2017.10.005"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040906"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.02.022"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2009.08.006"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8987.2"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201010\u2010187179"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2011.01302.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6039171"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01355"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101098"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102893"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20600"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.013"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.025"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010022\u201001279\u20108"},{"key":"e_1_2_11_30_1","volume-title":"3rd Edition","author":"Federation T. M. S. I.","year":"2020"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.04.010"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.1.5"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102249.2010.04143.x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.12.006"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010012\u20100970\u20100"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1013"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474\u20109726.2012.00839.x"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(14)70305\u20109"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911461"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.4764"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10251"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110640"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027006"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8060575"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101631\u20104"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102014\u201015\u20102\u2010r29"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12435"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2021.04.008"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.11.005"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948299"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102093"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv412"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0502\u2010500"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq463"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504979102"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks042"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.2.574"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318165b239"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003952"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102011\u201002\u2010336552"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.37.7.1097"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms12128695"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1261"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202395"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2015.05.004"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2013.10.004"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201052001\u20102.00008\u2010X"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010020\u201001904\u2010z"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318230a17d"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12716"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201008140\u20107"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20913"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204471"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.01.005"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u2010510x(88)90130\u2010x"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.02.002"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600968"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13630"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00524"},{"key":"e_1_2_11_85_1","unstructured":"WHO.2022.Ageing and health.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/ageing\u2010and\u2010health."},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38902"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.07.013"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009234\u20106"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030706"}],"updated-by":[{"DOI":"10.1111\/acel.70129","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000}}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.14491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T21:25:17Z","timestamp":1757107517000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.14491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,2]]},"references-count":88,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/acel.14491"],"URL":"https:\/\/doi.org\/10.1111\/acel.14491","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1111\/acel.70129","asserted-by":"object"}]},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,2]]},"assertion":[{"value":"2024-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14491"}}