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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.