Proteostasis in aging and diabetic cardiomyocytes

Contact: Dr. Christiane Ott

Funding: DZHK, DFG, MWFK

Within this research focus we are investigating proteostasis in aging and metabolically challenged cardiomyocytes. We postulate that imbalanced proteostasis (balance of protein synthesis and degradation) in aged cardiomyocytes contributes to cellular dysfunction and finally to organ failure. In previous studies on redox- and age-related changes in proteostasis, our findings revealed an age- and disease-associated decline of proteolysis in fibroblasts, hepatocytes, astrocytes and various cell lines.

Currently, we are investigating the impact of impaired proteostasis on functionality of cardiomyocytes under various challenges. In parallel to the analysis of metabolic changes (blood glucose, body and heart fat, blood pressure) we are determining biochemical alterations inside the cells. Methods for the isolation of metabolically challenged and aged cells as well as a new method for the analysis of cardiomyocyte contractility were successfully established and are already in use.

Regarding our studies on proteolysis, we are focusing on the proteasomal and autophagic-lysosomal systems during aging and/or in cardiovascular or metabolic stress situations. Additionally, direct metabolic changes in cardiomyocytes, such as substrate usage and mitochondrial respiration, are studied, particularly focusing on the diabetic heart. Since an imbalanced proteostasis due to impaired proteolysis might reduce cardiac function, we try in several projects to improve cardiomyocyte contractility by stimulating proteolysis using nutritional relevant components.