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

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 1131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7±5.9 years), 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.

Torque teno virus viral load predicts SARS‐CoV‐2 vaccine response in kidney transplant recipients

“…HIV patients, 23 and inversion of the CD4/CD8 ratio showing an immune risk phenotype in healthy individuals. 24 Higher TTV VL have been shown to be a strong predictor of mortality in the elderly, 25,26 as well as a marker of worse survival and complications in hematopoietic stem cell transplantation 27 and clinical deterioration in critically ill patients. 28 In patients with rheumatoid arthritis receiving immunomodulation with biological compounds, TTV levels helped predict clinical response.…”

“…In other populations, TTV VL and T‐cell responses have been linked, with high TTV loads associated with poor T‐cell proliferative capacity in allogeneic hematopoietic stem cell transplantation recipients, 22 diminished CD4 + T‐cell recovery in HIV patients, 23 and inversion of the CD4/CD8 ratio showing an immune risk phenotype in healthy individuals 24 . Higher TTV VL have been shown to be a strong predictor of mortality in the elderly, 25,26 as well as a marker of worse survival and complications in hematopoietic stem cell transplantation 27 and clinical deterioration in critically ill patients 28 . In patients with rheumatoid arthritis receiving immunomodulation with biological compounds, TTV levels helped predict clinical response 29 .…”

The mysterious anelloviruses: investigating its role in human diseases

“…The increase in the amount of virus load in the host is related to the decrease in the quality of the host’s immune system due to aging. It is possible that this increase in viremia can lead to immune system disorders and increased mortality in the elderly population [ 19 , 121 ]. Also, TTV has beneficial effects on the immune system of infants, which will ultimately cause the growth and maturation of their immune system [ 7 , 122 ].…”

Spreading Senescent Cells’ Burden and Emerging Therapeutic Targets for Frailty

“…While there is mounting evidence that the gut microbiota profiles of frail older individuals differ from those of non-frail older people, research regarding the virome is still in its early stages. A recent study [ 86 ] has shown the differences between frail and non-frail individuals in the abundance of a specific circulating virome component, torquetenovirus (TTV), a commensal human annellovirus representing the most abundant component of human virome. High TTV viremia has also been associated with an increased risk for all-cause mortality in an Italian elderly population study [ 87 ].…”