{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:24:35Z","timestamp":1792898675276,"version":"4.5.0"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"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":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Torquetenovirus (TTV) is a prevalent virus whose clinical significance remains unclear, potentially linked to immunosenescence. This study examines TTV species in relation to immune impairment, inflammation, and cellular stress response in aging. A subset of recruited age\u2010stratified individuals (RASIG) from the MARK\u2010AGE study was divided into three groups: Cohort 1\u2009A (healthy young adults), Cohort 1B (older adults with mild immune decline), and Cohort 1\u2009C (older adults with marked immune impairment). Analyses included TTV load, species diversity, lymphocyte subpopulations, inflammatory markers, Poly\u2010(ADP\u2010ribose) polymerase (PARP\u20101) expression\/activity. Alpha\u2010 and beta\u2010diversity analyses showed the highest TTV species diversity in Cohort 1\u2009C, with significant cohort\u2010dependent differences and partially cohort\u2010specific clustering patterns. Increased TTV species number correlated with higher TTV load, elevated CMV IgG levels, and greater immune impairment risk. Specific TTV species were associated with CD4\/CD8, and reduced T\u2010cell receptor excision circles, suggesting impaired T\u2010cell homeostasis. TTV viremia positively correlated with C\u2010reactive protein (CRP) and \u03b12\u2010macroglobulin. PARP\u20101 expression and activity increased in individuals with higher TTV diversity, particularly in the presence of TTV9 and TTV20. TTV load and species diversity are associated with immunosenescence, inflammation, and PARP\u20101 activation suggesting their potential as biomarkers of age\u2010related immune decline. Longitudinal studies are needed to clarify underlying mechanisms.<\/jats:p>","DOI":"10.1002\/jmv.70656","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T13:39:01Z","timestamp":1761226741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging"],"prefix":"10.1002","volume":"97","author":[{"given":"Federica","family":"Novazzi","sequence":"first","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"},{"name":"Laboratory of Microbiology, ASST Sette Laghi Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro Giorgio","family":"Spezia","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases, Lazzaro Spallanzani\u2010 IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-0703","authenticated-orcid":false,"given":"Francesca Drago","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, ASST Sette Laghi Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Paolo","family":"Genoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"},{"name":"Laboratory of Microbiology, ASST Sette Laghi Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo Antonio","family":"Grossi","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, ASST Sette Laghi Varese Italy"},{"name":"Infectious and Tropical Diseases Unit, ASST\u2010Sette Laghi Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicasio","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"},{"name":"Laboratory of Microbiology, ASST Sette Laghi Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8442-1763","authenticated-orcid":false,"given":"Marco","family":"Malavolta","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA Ancona Italy"},{"name":"Department of Clinical and Molecular Sciences, Disclimo Universit\u00e0 Politecnica delle Marche Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Balietti","sequence":"additional","affiliation":[{"name":"Center for Neurobiology of Aging, IRCCS INRCA Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Piacenza","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Marcozzi","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretta Veronica","family":"Badillo Pazmay","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0322-0282","authenticated-orcid":false,"given":"Laura","family":"Cianfruglia","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"B\u00fcrkle","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Group, Department of Biology University of Konstanz Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Moreno\u2010Villanueva","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Group, Department of Biology University of Konstanz Konstanz Germany"},{"name":"Department of Sport Science, Human Performance Research Centre University of Konstanz Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn E. 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