Prevalence and Loads of Torquetenovirus in the European MARK-AGE Study Population

Abstract

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.

Torque Teno Virus load in lung cancer patients correlates with age but not with tumor stage

“…In our patient population, older individuals had significantly higher TTV DNA levels. This finding is in line with previous investigations on smaller cohorts and with a large survey for markers of aging (MARK-AGE) [ 29 – 31 ]. Indeed, in the MARK-AGE study only age and gender showed a significant association with TTV loads but no blood based routine laboratory parameter did.…”

“…Haloschan et al found lower TTV levels for women under the age of 30 when compared to men [ 31 ] but our patient cohort includes only patients older than 30 years of age. Confirming the findings of the MARK-AGE study [ 29 ], TTV DNA levels showed no significant association with the amount of hemoglobin, albumin, CRP or WBC in our cohort.…”

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

“…This hypothesis was also confirmed by the observation that the replication of vesicular stomatitis virus is impaired both in primary and tumor senescent cells in comparison to non-senescent cells [54]. Many studies have described a higher prevalence or increased circulating viral load of some viruses, such as cytomegalovirus (CMV) [55] and Torquetenovirus (TTV) [56,57], with aging. The increased grade of inflammation associated with this phenomenon and the association with mortality of TTV and CMV in the elderly highlights the possible involvement of cellular senescence.…”

Survey of Viral Reactivations in Elite Athletes: A Case-Control Study

“…TTV infections are acquired soon after birth and result in chronic asymptomatic viremia [24] that can be significantly elevated in immunosuppression [18,25] and immune senescence [20,21,26]. Indeed, in immunocompromised individuals, such as transplant recipients [17], the average copy numbers can be as high as 10 10 /mL of plasma [18].…”

“…While local bursts of replication may be common even in healthy individuals, the presence of HHV DNA in sera is a strong indicator of immunosuppression [12][13][14][15][16][17]. TTV infections, on the other hand, result in asymptomatic, lifelong low-level viremia that can be significantly increased in immunosuppression [18,19] and immunosenescence [20,21].…”