Project Details
Projekt
Exploring the impact of intravenous iron therapies on biological aging of the heart
Applicant
Sophia Walter
Subject Area
Nutritional Sciences
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 573933204
Cardiac aging is an undeniable risk factor for cardiovascular diseases, the current leading cause of death worldwide. In recent years, a dysregulated iron homeostasis gained recognition as one factor contributing to age-associated degeneration of the heart. Since iron deficiency is common worldwide, the use of iron therapies to treat its deficiency has gained importance. These therapies rapidly stabilize the body’s iron level; however, recent studies indicate that the drugs can lead to accumulation of labile iron in the heart, potentially damaging the muscle. Interestingly, iron remains elevated in the heart even after blood tests return back to iron deficiency levels, suggesting a risk of cumulative damage by repeated iron therapies. Accordingly, it is hypothesized, that repeated intravenous iron therapies in iron deficiency result in a build-up of cardiac iron, ultimately accelerating aging of the heart. The proposed mechanism is based on the increase of non-transferrin bound iron (NTBI) released from iron drugs, which can be taken up by transporters bypassing the normal iron regulatory mechanisms. This can lead to an increase in cardiomyocyte’s labile iron pool, promoting oxidative damage of essential cellular components. In iron overload conditions such as hemochromatosis, overload is directly linked to cardiac toxicity and an aging-associated cardiac phenotype. Accordingly, the rise in cardiac iron induced by intravenous iron might ultimately manifest as cardiac aging, including cardiac fibrosis, hypertrophy and impaired contractile function. As the commonly used iron therapies ferric carboxymaltose and ferric derisomaltose differ in their effects on the rise in NTBI, it is hypothesized that the drugs vary in their effect on aging of the heart. Therefore, this project aims to investigate the impact of different intravenous iron therapies on cardiac iron metabolism and its contribution to cardiac aging using human, murine and cell culture models. While serum samples from subjects receiving intravenous iron therapies will provide information about the changes in serum aging markers, a mouse model will be used to investigate the potential cumulative build-up of cardiac iron and its effect on cardiac aging markers. Cultivated cardiomyocytes will reveal insights into the underlying mechanisms and introduce e.g. iron chelators as potential therapeutic strategies. With this, the aim is to determine consequences of currently used intravenous iron therapies on cardiac health and potentially identify strategies to minimize risks associated with these treatments.
DFG Programme
WBP Fellowship
International Connection
United Kingdom
