{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T06:20:06Z","timestamp":1774765206988,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","award":["A18\u20101052"],"award-info":[{"award-number":["A18\u20101052"]}],"id":[{"id":"10.13039\/100010877","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>Due to the increased burden of non\u2010AIDS\u2010related comorbidities in people living with HIV (PLHIV), identifying biomarkers and mechanisms underlying premature aging and the risk of developing age\u2010related comorbidities is a priority. Evidence suggests that the plasma proteome is an accurate source for measuring biological age and predicting age\u2010related clinical outcomes. To investigate whether PLHIV on antiretroviral therapy (ART) exhibit a premature aging phenotype, we profiled the plasma proteome of two independent cohorts of virally suppressed PLHIV (200HIV and 2000HIV) and one cohort of people without HIV (200FG) using O\u2010link technology. Next, we built a biological age\u2010prediction model and correlated age advancement (the deviation of the predicted age from the chronological age) with HIV\u2010related factors, comorbidities, and cytokines secreted by immune cells. We identified a common signature of 77 proteins associated with chronological age across all cohorts, most of which were involved in inflammatory and senescence\u2010related processes. PLHIV showed increased age advancement compared to people without HIV. In addition, age advancement in the 2000HIV cohort was positively associated with prior hepatitis C and cytomegalovirus (CMV) infections, non\u2010AIDS\u2010related comorbidities, ART duration, cumulative exposure to the protease inhibitor Ritonavir, as well as higher production of monocyte\u2010derived proinflammatory cytokines and chemokines and lower secretion of T\u2010cell derived cytokines. Our proteome\u2010based predictive model is a promising approach for calculating the age advancement in PLHIV. This will potentially allow for further characterization of the pathophysiological mechanisms linked to accelerated aging and enable monitoring the effectiveness of novel therapies aimed at reducing age\u2010related diseases in PLHIV.<\/jats:p>","DOI":"10.1111\/acel.14468","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T06:47:35Z","timestamp":1736923655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Plasma Proteomic Signature as a Predictor of Age Advancement in People Living With <scp>HIV<\/scp>"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6519-2486","authenticated-orcid":false,"given":"Adriana","family":"Navas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliki","family":"Matzaraki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise E.","family":"van Eekeren","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc J. T.","family":"Blaauw","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"},{"name":"Department of Internal Medicine and Infectious Diseases Elizabeth\u2010Tweesteden Ziekenhuis  Tilburg The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert L.","family":"Groenendijk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"},{"name":"Department of Internal Medicine, ErasmusMC Erasmus University  Rotterdam The Netherlands"},{"name":"Department of Medical Microbiology and Infectious Diseases, ErasmusMC Erasmus University  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilhelm A. J. W.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"},{"name":"Department of Internal Medicine and Infectious Diseases OLVG  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maartje","family":"Jacobs\u2010Cleophas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9ssica C.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 J. A. M.","family":"van der Ven","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo A. B.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"},{"name":"Department of Medical Genetics Iuliu Hatieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboudumc Radboud University  Nijmegen The Netherlands"},{"name":"Department of Immunology and Metabolism, Life and Medical Sciences Institute University of Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203350"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095192"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000599"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1506264112"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-020-05593-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104488"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402197"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2023.1112109"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(16)30020-2"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25847"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8041616"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203625"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000002063"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61809-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101743"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098117"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab338"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(21)00006-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt531"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11030468"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers8080073"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv277"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2016.04.006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz206"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02476-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.2.1480"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13750"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01502-8"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2021.111228"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/23337214211046419"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017050574"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-01053-0"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.003"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4140"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06802-1"},{"key":"e_1_2_9_37_1","unstructured":"Prada C. 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