Evidence map›Paper›PMID 41128646›Full record

ArticleJournal of medical virology2025

TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging.

Federica Novazzi, Pietro Giorgio Spezia, Francesca Drago Ferrante, Angelo Paolo Genoni, Paolo Antonio Grossi, Nicasio Mancini, Marco Malavolta, Marta Balietti, Francesco Piacenza, Serena Marcozzi and 26 more

Abstract read
In one paragraph

Article in Journal of medical virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Federica NovazziDepartment of Medicine and Technological Innovation, University of Insubria, Varese, Italy.
Pietro Giorgio SpeziaLaboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani- IRCCS, Rome, Italy.
Francesca Drago FerranteLaboratory of Microbiology, ASST Sette Laghi, Varese, Italy.ORCID 0000-0003-4950-0703
Angelo Paolo GenoniDepartment of Medicine and Technological Innovation, University of Insubria, Varese, Italy.
Paolo Antonio GrossiLaboratory of Microbiology, ASST Sette Laghi, Varese, Italy.
Nicasio ManciniDepartment of Medicine and Technological Innovation, University of Insubria, Varese, Italy.
Marco MalavoltaAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.ORCID 0000-0002-8442-1763
Marta BaliettiCenter for Neurobiology of Aging, IRCCS INRCA, Ancona, Italy.
Francesco PiacenzaAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.
Serena MarcozziAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.
Carlo FortunatoAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.
Gretta Veronica Badillo PazmayAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.
Laura CianfrugliaAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.ORCID 0000-0002-0322-0282
Alexander BürkleMolecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany.
María Moreno-VillanuevaMolecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany.
Martijn E T DolléCentre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Eugène JansenCentre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Tilman GruneDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
Efstathios S GonosNational Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
Claudio FranceschiInstitute of Biogerontology, Lobachevsky State University, Nizhny, Novgorod, Russia.
Miriam CapriDepartment of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Michele ZampieriDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Paola CaiafaDepartment of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy.
Fabio CiccaroneDepartment of Biology, University of Rome "Tor Vergata", Rome, Italy.
Anna RealeDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Birgit WeinbergerInstitute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria.
Ewa SikoraLaboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Florence Debacq-ChainiauxURBC-NARILIS, University of Namur, Namur, Belgium.
Wolfgang StuetzDepartment of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, Stuttgart, Germany.
Mikko HurmeFaculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
P Eline SlagboomDepartment of Molecular Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands.
Jürgen BernhardtBioTeSys GmbH, Esslingen, Germany.
Fabiola OlivieriAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.
Fabio FilippiniDepartment of Translational Research, University of Pisa, Pisa, Italy.
Fabrizio MaggiLaboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani- IRCCS, Rome, Italy.
Robertina GiacconiAdvanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.

Funding

This study was supported by the European Union - Next Generation EU - PNRR M6C2 - Investimento 2.1 Valorizzazione e potenziamento della Ricerca biomedica del SSN PNRR-MAD-2022-12376334 VIROMA project.
6 · The paper itself

Abstract

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-stratified individuals (RASIG) from the MARK-AGE study was divided into three groups: Cohort 1 A (healthy young adults), Cohort 1B (older adults with mild immune decline), and Cohort 1 C (older adults with marked immune impairment). Analyses included TTV load, species diversity, lymphocyte subpopulations, inflammatory markers, Poly-(ADP-ribose) polymerase (PARP-1) expression/activity. Alpha- and beta-diversity analyses showed the highest TTV species diversity in Cohort 1 C, with significant cohort-dependent differences and partially cohort-specific 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-cell receptor excision circles, suggesting impaired T-cell homeostasis. TTV viremia positively correlated with C-reactive protein (CRP) and α2-macroglobulin. PARP-1 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-1 activation suggesting their potential as biomarkers of age-related immune decline. Longitudinal studies are needed to clarify underlying mechanisms.

Indexed as

AgingDNA Virus InfectionsTorque teno virusAdultAgedAged, 80 and overBiomarkersCohort StudiesFemaleHumansImmunosenescenceMaleMiddle AgedPoly (ADP-Ribose) Polymerase-1Viral LoadYoung AdultBiomarkersPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1agingimmunosenescenceinflammationPARP‐1TTV species

Identifiers

PMID41128646
PMCPMC12548562

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.