Objective Here, we propose a program to identify the role of mTOR and autophagy dependent epigeneticmodifications during kidney aging. We have assembled a unique set of complementary mouse models including kidney specific and timely inducible autophagy and mTOR deficient mice. For the detailed molecular analysis of transgenic podocyte tissue, we have generated a double-labeled transgenic mouse model, where podocytes expressing green fluorescent protein are contrasted by other kidney cells expressing red fluorescent protein. Using this mouse model, we have pioneered a cell sorter based purification of glomerular podocytes from kidney single cell suspensions, which allows us to perform the first epigenetic analysis of aged and transgenically modified podocytes. mTOR and / or autophagy dependent gene expression signatures, histone modifications and chromatin-remodeling patterns associated with kidney aging in transgenic and wildtype mice will be identified. We recently showed that mTOR hyperactivation at early stages of diabetic nephropathy determines the progressive course of the disease. We now hypothesize that transient mTOR hyperactivation may induce epigenetic modifications representing the clinically observed, but still unresolved “metabolic memory” of diabetic nephropathy. Insummary, this project aims to elucidate fundamental biological mechanisms of kidney aging. This may ultimately aid in risk prediction and improved targeted medical interventions to promote healthy aging and to prevent chronic kidney diseases such as diabetic nephropathy. Fields of science medical and health sciencesclinical medicineendocrinologydiabetesdiabetic nephropathynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsepigeneticsmedical and health sciencesclinical medicinenephrologykidney diseases Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2011-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator UNIVERSITAETSKLINIKUM FREIBURG EU contribution € 100 000,00 Address HUGSTETTER STRASSE 49 79106 Freiburg Germany See on map Region Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Gerhard Henninger (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
