SP8

Principal Investigator: Andreas Simm (Clinic for Heart and Thoracic Surgery, University Hospital Halle and MLU Halle-Wittenberg)

Yazan Dalilah (PhD): Histone glycation, cellular senescence and vascular aging - from molecular mechanism to translation

Merve Kuru-Schors (PhD): RAGE-independent induction of cellular signaling in the cardiovascular system by AGEs

Parisa Ghaffari Makhmalbaf (PhD): Hypoxie dependence of senescence induction by glycative substances in the cardiovascular system

Ana-Maria Eberl (MD): Testing scores and their predictive value with regard to postoperative outcome measured in morbidity and (bio-)functionality in older patients undergoing cardiac surgery

Shubhangi Karande (PhD): Cellular and molecular impact of nuclear protein glycation

Persistent epigenetic modifications, such as histone acetylation, can change gene expression and the ageing process. Histone glycation was found to change with age in mice and may compete with acetylation since both modifications target the same amino acid. As young cells mainly get their energy from mitochondrial ATP generation, while senescent cells obtain ATP from glycolysis leading to increased formation of glycating agents such as dicarbonyls, we want to test the hypothesis that dicarbonyl-induced glycation has an impact on epigenetic regulation.

After identification of glycated nuclear proteins by mass spectrometry, the in vivo-relevance of these findings will be tested in our ageing mouse cohort and in patient samples. Depending on the proteins identified, their role in cell signaling, gene transcription / translation and regulation will be analyzed. Molecular consequence of the glycation on protein function and structure will be analyzed by structural biology methods including NMR spectroscopy.