In the first phase of TraceAge, we established a human serum TE fingerprint, consisting of the serum TE concentrations of Se, I, Mn, Fe, Zn, Cu augmented by four functional TE markers. These enable us to specifically characterize and describe a particular nutritional or health status. In the second phase of TraceAge, we aim to prove the validity of loosely bound Cu as well as thyroid hormones for use as further functional TE biomarkers, which will add pivotal information to the serum TE fingerprint. Therefore, serum of both previous and new human cohorts will be analysed and mouse studies will be employed. In addition, we intend to establish new cellular and tissue TE markers.
A special focus of our project work is set to disease-related and age-specific TE fingerprints by assessing a broad spectrum of TE markers in diseased humans as well as in inflamed and aged mice. Here, we hypothesize that suboptimal TE supply (established in mice in the first TraceAge phase) will become detrimental under conditions of chronic inflammation and aging, resulting among others in genomic instability. We are in particular interested in the impact of aging and suboptimal TE supply on the brain, likely both factors facilitating neurodegeneration by disturbing TE homeostasis. Eventually, neuronal genomic instability results as a consequence of impaired DNA repair and DNA damage response. Besides mouse studies, primary brain-barrier models as well as a human astrocyte/neuron co-culture will be applied to mechanistically characterize the impact of the TE status on neurodegeneration. In summary, we aim to identify TE fingerprints, including functional TE markers, which have the potential to become a reliable predictive tool for the risk to develop age-related diseases.