TY - JOUR
T1 - Prevalence and Loads of Torquetenovirus in the European MARK-AGE Study Population
AU - Giacconi, Robertina
AU - Maggi, Fabrizio
AU - Macera, Lisa
AU - Spezia, Pietro Giorgio
AU - Pistello, Mauro
AU - Provinciali, Mauro
AU - Piacenza, Francesco
AU - Basso, Andrea
AU - Bürkle, Alexander
AU - Moreno-Villanueva, María
AU - Dollé, Martijn E.T.
AU - Jansen, Eugène
AU - Grune, Tilman
AU - Stuetz, Wolfgang
AU - Gonos, Efstathios S.
AU - Schön, Christiane
AU - Bernhardt, Jürgen
AU - Grubeck-Loebenstein, Beatrix
AU - Sikora, Ewa
AU - Dudkowska, Magdalena
AU - Janiszewska, Dorota
AU - Toussaint, Olivier
AU - Debacq-Chainiaux, Florence
AU - Franceschi, Claudio
AU - Capri, Miriam
AU - Hervonen, Antti
AU - Hurme, Mikko
AU - Slagboom, Eline
AU - Breusing, Nicolle
AU - Mocchegiani, Eugenio
AU - Malavolta, Marco
N1 - Publisher Copyright:
© The Author(s) 2019.
PY - 2020/9/25
Y1 - 2020/9/25
N2 - Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians [GO]) and premature (Down syndrome [DS]) immunosenescence. The TTV load was positively associated with age, cytomegalovirus (CMV) antibody levels, and the Cu/Zn ratio and negatively associated with platelets, total cholesterol, and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (Randomly Recruited Age-Stratified Individuals From The General Population) populations. In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with ≥4log TTV copies/mL had a higher risk of having a CD4/CD8 ratio<1 than those with lower viremia (odds ratio [OR] = 2.85, 95% confidence interval [CI]: 1.06-7.62), as well as reduced CD3+ and CD4+T-cells compared to males with lower replication rates (<4log), even after adjusting for CMV infection. In summary, differences in immune system preservation are reflected in the models of delayed and premature immunosenescence, displaying the best and worst control over TTV replication, respectively. In the general population, TTV loads were negatively associated with CD4+ cell counts, with an increased predisposition for an inverted CD4/CD8 ratio for individuals with TTV loads ≥4log copies/mL, thus promoting an immune risk phenotype.
AB - Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians [GO]) and premature (Down syndrome [DS]) immunosenescence. The TTV load was positively associated with age, cytomegalovirus (CMV) antibody levels, and the Cu/Zn ratio and negatively associated with platelets, total cholesterol, and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (Randomly Recruited Age-Stratified Individuals From The General Population) populations. In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with ≥4log TTV copies/mL had a higher risk of having a CD4/CD8 ratio<1 than those with lower viremia (odds ratio [OR] = 2.85, 95% confidence interval [CI]: 1.06-7.62), as well as reduced CD3+ and CD4+T-cells compared to males with lower replication rates (<4log), even after adjusting for CMV infection. In summary, differences in immune system preservation are reflected in the models of delayed and premature immunosenescence, displaying the best and worst control over TTV replication, respectively. In the general population, TTV loads were negatively associated with CD4+ cell counts, with an increased predisposition for an inverted CD4/CD8 ratio for individuals with TTV loads ≥4log copies/mL, thus promoting an immune risk phenotype.
KW - Aging
KW - CD4/CD8 ratio
KW - Down syndrome
KW - Immunosenescence
KW - TTV
UR - http://www.scopus.com/inward/record.url?scp=85091807046&partnerID=8YFLogxK
U2 - 10.1093/gerona/glz293
DO - 10.1093/gerona/glz293
M3 - Article
C2 - 31838498
AN - SCOPUS:85091807046
SN - 1079-5006
VL - 75
SP - 1838
EP - 1845
JO - The journals of gerontology. Series A, Biological sciences and medical sciences
JF - The journals of gerontology. Series A, Biological sciences and medical sciences
IS - 10
ER -