The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress.

Abstract

Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance. In this observational longitudinal study, we examined in peripheral blood mononuclear cells (PBMCs), whether MHI predicted changes in telomerase activity over a 9-month period, thus impacting telomere maintenance over this same period of time. We secondarily examined the role of chronic stress, by comparing these relationships in mothers of children with an autism spectrum disorder (caregivers) vs. mothers of a neurotypical child (controls). Here we show that both chronic stress exposure and lower MHI independently predicted decreases in telomerase activity over the subsequent 9 months. Finally, changes in telomere length were directly related with changes in telomerase activity, and indirectly with MHI and chronic stress, as revealed by a path analysis. These results highlight the potential role of chronic stress and MHI as drivers of telomere attrition in human PBMCs, through an impairment of both energy-transformation capacity and telomerase production.