Association of Torquetenovirus Viremia with Physical Frailty and Cognitive Impairment in Three Independent European Cohorts.

Tilman Grune, Lisa Macera, Pietro Giorgio Spezia, María Moreno-Villanueva, Stefano Bonassi, Vanessa Valdiglesias, Joao Paulo Teixeira, Martijn E T Dollé, M Liset Rietman, Eugène Jansen, Fabrizio Maggi, Claudio Franceschi, Miriam Capri, Birgit Weinberger, Wolfgang Stuetz, Eduardo Pásaro, Ana Maseda, Laura Lorenzo-López, José Carlos Millán-Calenti, Nicolle Breusing, Efstathios S Gonos, P Eline Slagboom, Robertina Giacconi, Mauro Provinciali, Francesco Piacenza, Christiane Schön, Jürgen Bernhardt, Ewa Sikora, Alexander Bürkle, Marco Malavolta, Olivier Toussaint, Florence Debacq-Chainiaux, Antti Hervonen, Mikko Hurme, Blanca Laffon, Solange Costa, Armanda Teixeira-Gomes

Journal: Gerontology 2023;69(6):684-693

PMID: 36538907

Full Text on S. Karger AG, Basel, Switzerland View on PubMed

Abstract

INTRODUCTION

Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment.

METHODS

TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years).

RESULTS

TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06-10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14-5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000-1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females.

CONCLUSIONS

These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.

Address: Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy.; Grupo DICOMOSA, CICA - Centro Interdisciplinar de Química e Bioloxía, Departamento de Psicología, Facultad de Ciencias de la Educación, Campus Elviña s/n, Universidade da Coruña, A Coruña, Spain.; Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain.; Environmental Health Department, National Institute of Health Doutor Ricardo Jorge, Porto, Portugal.; EPIUnit -Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.; Department of Medicine and Surgery, University of Insubria, Varese, Italy.; Department of Translational Research, University of Pisa, Pisa, Italy.; Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany.; Human Performance Research Centre, Department of Sport Science, University of Konstanz, Konstanz, Germany.; Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy.; Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy.; Grupo NanoToxGen, CICA - Centro Interdisciplinar de Química e Bioloxía, Departamento de Biología, Facultad de Ciencias, Campus A Zapateira s/n, Universidade da Coruña, A Coruña, Spain.; Centre for Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.; Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.; Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.; National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.; Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum University of Bologna, Bologna, Italy.; Institute of Information Technologies, Mathematics and Mechanics, Lobachevsky University, Nizhniy Novgorod, Russian Federation.; Interdepartmental Center - Alma Mater Research Institute on Global Challenges and Climate Change - University of Bologna, Bologna, Italy.; Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.; Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.; Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, Stuttgart, Germany.; URBC-NARILIS, University of Namur, Namur, Belgium.; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.; BioTeSys GmbH, Esslingen, Germany.; Department of Applied Nutritional Science/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.; Gerontology and Geriatrics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña, A Coruña, Spain.

DOI: 10.1159/000528169

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MeSH Terms: Female, Aged, Humans, Aged, 80 and over, Frailty, Torque teno virus, Viremia, Frail Elderly, Geriatric Assessment, Cognitive Dysfunction