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Trace element (TE) fingerprinting and genomic stability

Project Summary

Nowadays the lack of suitable biomarkers for TE status massively limits our capacity to assess the relationship between dietary TE intake, homeostasis and health and thus, disables us to recommend adequate age-specific intake levels for the respective TEs in both healthy and diseased humans. We hypothesize that a combined analysis of the TE profile consisting of the TE (Cu, Zn, Mn, Fe, Se, I) serum levels and the serum TE functional fraction markers (loosely bound Cu, low molecular mass Zn and Mn) contributes strongly to a reliable description of the health status. To prove our assumption TE profiles and TE fraction markers will be quantified in human serum samples of the EPIC-Potsdam cohort and the TEhab cohort by means of an optimized sample preparation followed by highly sensitive and selective inductively coupled plasma tandem mass spectrometry. Moreover, based on recent literature but also our own previous studies, we hypothesize that a disturbed TE homeostasis contributes to the aging process among others by a disturbance of DNA repair processes and thus genomic instability. To provide evidence for this assumption we will study the impact of the TE status in young and aged mice on genomic stability and analyze whether these age-dependent differences can be recapitulated by feeding “old-adapted” TE profiles to young mice. Here we will quantify TE profiles and functional TE markers (fraction markers, non-targeted metabolomics) as well as genomic stability related markers including DNA lesions, poly(ADP-ribosyl)ation, base excision repair efficiency, global DNA (hydroxyl)methylation and telomere length in the blood (serum) and liver of mice. Based on the proposed interaction, we believe that the TE fingerprint in combination with functional markers of genomic integrity could have the potential to provide a more reliable prediction for the risk of developing age-related diseases.