{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:08:00Z","timestamp":1784610480301,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Long\u2010living individuals (LLIs) possess remarkable genetic resilience, characterized by protective variants that confer immune robustness and resistance to age\u2010related diseases. The longevity\u2010associated variant of BPIFB4 (LAV\u2010BPIFB4), enriched in centenarians, demonstrated pleiotropic benefits including reduced inflammation, cardiovascular protection, and immune system rejuvenation. However, the molecular mechanisms underlying these protective effects remain incompletely understood. Here, we revealed that LAV\u2010BPIFB4 fundamentally reshaped the immune features of platelets to establish enhanced immunomodulatory capacity through CD47 upregulation. Of note, centenarians displayed an elevated percentage of circulating CD47\n                    <jats:sup>+<\/jats:sup>\n                    reticulated platelets (RPs), a condition mimicked by LAV\u2010BPIFB4 carriers which exhibited significantly elevated CD47 levels both on RPs and mature platelets' surface. In agreement with an early acquirement of CD47 overexpression, MEG\u201001 megakaryoblastic cells overexpressing LAV\u2010BPIFB4 produced CD47\u2010high platelet\u2010sized particles. Functionally, platelets from LAV carriers suppressed monocyte activation and inflammatory cytokine production through CD47\u2010dependent mechanisms, selectively reducing p38 MAPK activation while leaving NF\u2010\u03baB signaling largely unaffected in response to LPS. rhLAV\u2010BPIFB4 administration in\u00a0vivo increased CD47 on murine platelets and reduced, ex\u00a0vivo, LPS\u2010induced monocyte activation, validating cross\u2010species therapeutic potential. Critically, rhLAV\u2010BPIFB4 protein phenocopies genetic effects, rapidly increasing CD47 expression on wild\u2010type platelets through cytoskeleton\u2010dependent trafficking mechanisms and conferring enhanced anti\u2010inflammatory capacity. This might represent a translatable strategy to replicate some of the biological features associated with a longevity\u2010associated variant beyond genetic carriers. Our findings establish the platelet\u2010CD47\u2010monocyte axis as a pivotal pathway for healthy aging and reveal recombinant LAV\u2010BPIFB4 as a promising therapeutic approach for managing inflammaging and cardiovascular disease by harnessing the immune\u2010tuning capacity characteristic of exceptional longevity.\n                  <\/jats:p>","DOI":"10.1111\/acel.70602","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:47:32Z","timestamp":1782388052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The LAV\u2010BPIFB4\u2010Platelet\u2010CD47 Axis: A Novel Mechanism Associated With Immune Resilience in Longevity"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8035-4583","authenticated-orcid":false,"given":"Elena","family":"Ciaglia","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d University of Salerno  Fisciano Italy"},{"name":"Cardiovascular Research Unit IRCCS Multimedica  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Maria","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d University of Salerno  Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Lopardo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d University of Salerno  Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Montella","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d University of Salerno  Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Basile","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d University of Salerno  Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d University of Salerno  Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Maciag","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Unit IRCCS Multimedica  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Rescigno","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit AOU San Giovanni di Dio e Ruggi d'Aragona  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Damato","sequence":"additional","affiliation":[{"name":"Vascular Physiopathology Unit IRCCS Neuromed  Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Del Plato","sequence":"additional","affiliation":[{"name":"ASL Salerno\u2010Ospedale di Comunit\u00e0 di Roccadaspide  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Finizio","sequence":"additional","affiliation":[{"name":"Transfusion Medicine Unit\u2010 ASL Salerno\u2010Battipaglia Hospital  Battipaglia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Vecchione","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d University of Salerno  Fisciano Italy"},{"name":"Vascular Physiopathology Unit IRCCS Neuromed  Pozzilli 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