Interactions of essential trace elements in healthy and diseased elderly (TraceAge)

The homeostasis of trace elements (TE) is affected by nutritional intake, sex, age, and health status. However, interactions of TE under physiological and pathophysiological conditions are poorly characterized. Here we aim to characterize the TE status in women and men of different age (EPIC-Potsdam cohort). To this end, we will measure the TE profiles (Se, Cu, Zn, Mn, Fe, I) from serum along with novel and established biomarkers of the TE status. These data will be combined to establish age- and sex-specific TE fingerprints of German elderly, and help to identify genetic and environmental modifiers. In order to test the relevance of such TE fingerprints, patients with cardiovascular disease during hospitalized rehabilitation (TEhab cohort) will be studied as a paradigm of severe disease with strong changes in mobility and nutrition. To get further mechanistic insights we will study TE profiles and their functional interactions in different tissues from young and old male and female mice under TE-replete and TE-poor conditions. Treatments with TE combinations in mice and C. elegans will identify TE effects on aging, cellular signaling, neurodegeneration, and immune response as well as interactions with drugs and thyroid hormone metabolism. Our results will broaden the understanding of the importance of TE in health and disease. This will provide a basis for better care and future intervention studies to improve the TE status of seniors and to better protect them from degeneration and age-related diseases.

Our results from the first phase of TraceAge, obtained by studying in vitro models as well as the in vivo models mouse and C. elegans, indicate that a disturbed TE homeostasis impacts on the immune response, modulates the redox status, increases genomic stability and neurodegeneration, and thereby contributes to the aging process. Therefore, in the second phase we will focus especially on these factors. Besides further characterization of TE interactions and elucidation of underlying mechanisms, we are thus especially interested in studying inflammation, neurodegeneration, and aging-related diseases such as type 2 diabetes, cardiovascular disease, colon carcinoma, Alzheimer’s disease, and wound healing disorder in order to predict disease risks and develop preventive strategies. Next to model organisms, we therefore conduct analyses within the EPIC-Potsdam cohort and the WONDER-study (wound healing disorders and frailty in a clinical setting), facilitating establishment of age- and disease-specific TE profiles and fingerprints, and yielding functional and mechanistic insights. By analysis of TE, TE species, TE-related regulators and proteins in vivo as well as in vitro, we aim to deepen our understanding of how individual TE affect the absorption, metabolism and homeostasis of other TE. Mechanistically, this will be supported by studies in state-of-the-art models of the intestinal barrier, the blood-brain barrier and the blood-liquor barrier. In addition, the cross-talk of age-relevant factors like drugs, cytokines, and thyroid hormones with TE homeostasis will be evaluated in our human cohorts augmented by our in vitro and in vivo models.