{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:40:24Z","timestamp":1781739624367,"version":"3.54.5"},"reference-count":122,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cardiovascular morbidity and mortality rise precipitously during the 6th\u20139th decades of life, identifying aging as a critical risk factor. Simultaneously, older individuals are susceptible to severe viral infection, raising the question whether shared mechanisms exist that predispose to both cardiovascular disease (CVD) and failing anti-viral immunity. The aging process causes steady decline in immune fitness (immune aging), which undermines the ability to generate protective anti-viral immune responses. Paradoxically, the aging immune system supports unopposed inflammatory pathways (inflammaging), which exacerbates tissue inflammation in CVD, specifically atherosclerosis. Here, we review the current evidence of how innate and adaptive immune aging promotes tissue-destructive inflammation in atherosclerosis while failing to fight viral infections. Further, we consider how these two disease processes mutually influence each other. We propose that mounting an effective anti-viral response induces off-target bystander activation and exhausts immune cells, ultimately exacerbating CVD. Additionally, we explore how atherosclerotic CVD impacts innate immunity through epigenetic modification of hematopoietic precursors and metabolically conditioning immune cells, leading to a dysfunctional immune system that accelerates plaque inflammation while simultaneously impairing host defense.<\/jats:p>","DOI":"10.3390\/cells14221793","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:37:52Z","timestamp":1763131072000},"page":"1793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune Age, Cardiovascular Disease, and Anti-Viral Immunity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5098-7737","authenticated-orcid":false,"given":"Kevin-Phu C.","family":"Le","sequence":"first","affiliation":[{"name":"Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Cardiology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2274-1723","authenticated-orcid":false,"given":"Fahad","family":"Shuja","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorg J.","family":"Goronzy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2230-9802","authenticated-orcid":false,"given":"Cornelia M.","family":"Weyand","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Cardiology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.cger.2009.07.007","article-title":"The burden of cardiovascular disease in the elderly: Morbidity, mortality, and costs","volume":"25","author":"Yazdanyar","year":"2009","journal-title":"Clin. 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