{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:16:23Z","timestamp":1778508983066,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/15066\u20100"],"award-info":[{"award-number":["2018\/15066\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/11422\u20100"],"award-info":[{"award-number":["2019\/11422\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/04593\u20105"],"award-info":[{"award-number":["2022\/04593\u20105"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","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>\n                    HIV infection induces chronic immune activation, predisposing people living with HIV (PLWH) to early immunosenescence. It is essential to understand the mechanisms behind the senescence\u2010associated secretory phenotype (SASP). This study investigates the role of extracellular vesicles (EVs) in peripheral immunosenescence in HIV infection associated with SASP modulation. Biological and in silico analyses were performed to explore the crosstalk between EVs, miR\u201021\u20105p, and SASP. Plasma EVs from PLWH were isolated and used to stimulate peripheral blood mononuclear cells (PBMCs) to evaluate their potential to induce SASP. Mononuclear cells were transfected in\u00a0vitro to induce the production of EVs carrying specific miR\u201021\u20105p and assess their role in SASP induction. Inflammatory and senescence markers were analyzed using an immunoassay, flow cytometry, and RT\u2010qPCR. Biological verifications revealed that plasma EVs from PLWH predominantly induce SASP and drive IL\u20106 production in HIV\u2010uninfected PBMCs. We confirmed that miR\u201021\u20105p expression was increased in plasma EVs from chronically infected PLWH on antiretroviral therapy (ART). Furthermore, we demonstrated that EVs overexpressing miR\u201021\u20105p induced SASP, specifically increasing IL\u20106 levels. SASP\u2010associated cytokines were associated with PLWH with impaired CD4 T cell recovery and a higher prevalence of CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD57\n                    <jats:sup>+<\/jats:sup>\n                    T cells. We also corroborate that IP\u201010, IFN\u2010\u03b3, and IL\u20106 could be potential biomarkers for identifying PLWH at greater risk of immunosenescence. Our findings provide insights into EVs driving SASP\/IL\u20106 release, and this effect becomes more evident in EVs that carry miR\u201021\u20105p. This finding highlights a potential mechanism by which EVs and IL\u20106 contribute to peripheral immunosenescence in HIV\u2010uninfected cells.\n                  <\/jats:p>","DOI":"10.1111\/acel.70320","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:26:04Z","timestamp":1765185964000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular Vesicles Favor Early Peripheral Immunosenescence Through Modulation of the Senescence\u2010Associated Secretory Phenotype in\n                    <scp>HIV<\/scp>\n                    Infection"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3810-2534","authenticated-orcid":false,"given":"Ricardo Cardoso","family":"Castro","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5006-8869","authenticated-orcid":false,"given":"Humberto Doriguetto","family":"Gravina","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science Immunology and Epigenetics Laboratory, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3964-7496","authenticated-orcid":false,"given":"Fabr\u00edcia Helo\u00edsa Cavicchioli","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science Immunology and Epigenetics Laboratory, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0669-793X","authenticated-orcid":false,"given":"Yann","family":"Lamarre","sequence":"additional","affiliation":[{"name":"Center for Cell\u2010Based Therapy, Regional Blood Center of Ribeir\u00e3o Preto, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-5075","authenticated-orcid":false,"given":"Caroline","family":"Fontanari","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science Immunology and Epigenetics Laboratory, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-6822","authenticated-orcid":false,"given":"Bonita","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology and Biological Chemistry Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-268X","authenticated-orcid":false,"given":"Olesia","family":"Gololobova","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology and Neurology and the Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaohao","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology and Neurology and the Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-3698","authenticated-orcid":false,"given":"Fausto","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-0141","authenticated-orcid":false,"given":"Simone","family":"Kashima","sequence":"additional","affiliation":[{"name":"Center for Cell\u2010Based Therapy, Regional Blood Center of Ribeir\u00e3o Preto, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo 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