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 Ballietti, 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

Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy.Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy. · pubmed

Paper

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.

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Research summary

TTV species diversity and load are proposed as biomarkers of immune dysregulation associated with aging. The study addresses immune impairment and inflammation in the context of aging, which are critical factors in understanding and potentially mitigating age-related decline.

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