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.