Project Details
Projekt
Trace element (TE) fingerprinting, genomic stability and neurodegeneration
Applicant
Professorin Dr. Tanja Schwerdtle
Subject Area
Nutritional Sciences
Term
since 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 316442145
Nowadays, the role of trace elements (TE) in human health is of growing interest because TE dyshomeostasis is supposed to contribute to the increased incidence and severity of several age-related diseases, such as neurodegenerative diseases. However, the lack of well-defined, sensitive, and selective biomarkers to assess the status of TE in humans restricts the capacity to assess the relationship between dietary TE intake, homeostasis and health. In the first TraceAge phase, we established a human serum TE fingerprint, consisting of the serum concentrations of Se, I, Mn, Fe, Zn, Cu and thus far four TE functional markers, which enables us to describe a certain nutritional or health status. In the second TraceAge phase, project P5 aims to prove the validity of loosely bound Cu as well as thyroid hormones for use as functional markers, which will be added to the serum TE fingerprint. This is achieved by both the analysis of serum from previous and new human cohorts as well as mouse studies. Additionally, new cellular and tissue TE markers will be established. Moreover, a special focus will be given to disease-related and age-specific TE fingerprints by assessing all TraceAge markers in diseased humans as well as in inflamed and aged mice. Here, we hypothesize that a suboptimal TE supply (established in the first TraceAge phase) will become detrimental under conditions of chronic inflammation and aging, resulting in genomic instability among others. Under aging (and TE suboptimal) conditions we hypothesize that neurodegeneration originates from disturbed TE homeostasis causing genomic instability by affecting 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, this project (together with all other TraceAge projects) will identify TE fingerprints, which (in combination with other biomarkers) have the potential to become a reliable predictive tool for the risk to develop age-related diseases.
DFG Programme
Research Units
