Testing a novel hypothesis for a bioenergetic-endocrinological regulation of telomere dynamics

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It is becoming evident that being healthy and functional at old age largely depends on the conditions experienced during developmental phases. Accumulating evidence suggests that the footprint of impaired early development is embedded in the length of telomeres (TL) - complexes of DNA and proteins that form protective cups at the end of chromosome - which become shorter with progressing age and exposure to oxidative stress. Many mechanisms underlying patterns of TL attrition, as well as the causal consequences for organisms are still unresolved. One major phenomenon is the shortening effect that glucocorticoids (GCs) exert on TLs at different ontogenetic stages in both humans and animals. Thus far, the actions of GCs on TL have been viewed as negative side effects since these promote oxidative stress and down-regulate telomerase activity (an enzyme for maintaining TL length). However, GCs are vital hormones without which organisms would perish within hours. The logical question therefore is: why should GCs directly cause TL shortening? I am proposing the novel hypothesis that these hormones contribute to regulating TL length during times of increased energy need by saving resources needed for TL maintenance. For example, GCs inhibit the enzyme TORC1 (Target of Rapamycin Complex 1, a regulator of cell growth), which is involved in the control of TL length. However a bioenergetics perspective of the actions of GCs on TLs has never been addressed, even though it is in line with their fundamental role in mediating energy and life-history trade-offs. This new perspective would greatly increase our understanding of TL attrition under stressful conditions, and likely enable us to find ways to counteract the adverse consequences of shortened TL. The aim of the proposed study is to investigate whether TL dynamics are one mechanism by which energetic trade-offs are resolved in, at least sometimes, an adaptive way. In the proposed study I will manipulate the energetic state of great tit (Parus major) nestlings living in the wild. I will use an avian model because avian erythrocytes have functional mitochondria, which will allow me to repeatedly measure TL dynamics in blood. I will focus on an ontogenetic stage (growth) during which TL attrition is extensive, fast and can have long lasting repercussions to test whether:1. TL shortening is induced by high energy demands (growth and variation in food availability) by comparing TL length of nestlings supplemented with nucleotides with that of controls. The same question will be evaluated from a hormonal perspective by administering GC hormones, to test this pathway for TL regulation. 2. Within a certain range, TL shortening is adaptive by quantifying physiological condition (mitochondrial activity, AMP-activated protein kinase and oxidative stress), morphological traits (mass, body size) and behavioral responses (personality traits) in experimental and control nestlings.