TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging
Year: 2025
Type: article
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.
Source: Journal of Medical Virology
DOI: 10.1002/jmv.70656
Authors: Federica Novazzi, Pietro Giorgio Spezia, Francesca Drago Ferrante, Angelo Paolo Genoni, Paolo Antonio Grossi, Nicasio Mancini, Marco Malavolta, Marta Balietti, Francesco Piacenza, Serena Marcozzi, Carlo Fortunato, Gretta Veronica Badillo Pazmay, Laura Cianfruglia, Alexander Bürkle, María Moreno‐Villanueva, Martijn E. T. Dollé, Eugène Jansen, Tilman Grune, Efstathios S. Gonos, Claudio Franceschi, Miriam Capri, Michele Zampieri, Paola Caiafa, Fabio Ciccarone, Anna Reale, Birgit Weinberger, Ewa Sikora, Florence Debacq‐Chainiaux, Wolfgang Stuetz, Mikko Hurme, P. Eline Slagboom, Jürgen Bernhardt, Fabiola Olivieri, Fabio Filippini, Fabrizio Maggi, Robertina Giacconi
Institutions: University of Insubria, Aziende Socio Sanitarie Territoriale dei Sette Laghi, Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Marche Polytechnic University, Istituto Nazionale di Riposo e Cura per Anziani, University of Konstanz, National Institute for Public Health and the Environment, German Institute of Human Nutrition, National Hellenic Research Foundation, N. I. Lobachevsky State University of Nizhny Novgorod, University of Bologna, Sapienza University of Rome, University of Rome Tor Vergata, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Universität Innsbruck, Instytut Biologii Doświadczalnej im. Marcelego Nenckiego, Polish Academy of Sciences, University of Namur, Namur Research Institute for Life Sciences, University of Hohenheim, Tampere University, University of Tampere, Leiden University, Leiden University Medical Center, BioTeSys (Germany), University of Pisa
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,730
Funder: European Commission
Award: G2327242446
OpenAlex ID: W4415474295