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Cardiomyocyte function and trace element status during Aging: Role of Proteostasis

Project Summary

Iron (Fe) is essential for normal cellular functioning, but in excess, labile reactive Fe enhances oxidative stress, often resulting in a free radical-induced cell death. On the other hand, Fe is crucial for the energy production of cells, especially in cardiomyocytes possessing a high energy demand. In cardiomyocytes, Fe is also required for myoglobin function providing intracellular oxygen transport. Therefore, cardiomyocytes are highly vulnerable to disturbances of Fe metabolism. The functionality of the Fe metabolism is ensured by a number of proteins, which undergo a permanent turnover. Aging is characterized by malfunction of protein turnover, which is mainly due to reduced responses of the ubiquitin-proteasomal system and the autophagy-lysosomal system. This is a dominating process in aging and, therefore, a decline of proteostasis is a hallmark of the aging process. The goal of this project is to systematically investigate, how age-associated changes in proteostasis, in particular proteolytic pathways, effect trace element (TE) status and Fe metabolism-related proteins in cardiomyocytes in relation to cellular function.