DOXorubicin toxicity: a model to study the role of EPIgenetic mechanisms in induction of cell SENescence – DOX-EPISEN

The deleterious role of cellular senescence is well documented in cardiac and renal disorders and is linked with "inflammaging", i.e. release of pro-inflammatory cytokines and impairment in immune cell.
DOX-EPISEN aims to better understand the pathophysiology of cellular senescence-related systemic disorders when associated with factors such as aging, metabolic disorders and hypertension by assessing:
- The impact of nutritional (energy or salt surplus) and environmental (physiological aging) stressors that can modulate cellular senescence and affect the rate of inflammaging in two target organs (heart and kidney) in a murine model of premature aging induced by doxorubicin (DOX) and in a cohort of DOX-treated patients
- The role of epigenetic reprogramming in the induction of cellular senescence in cellular models focusing on immune cells (bone-marrow derived macrophages and rtissue-reident macrophages in teh heart and kidney) and endothelial cells derived from teh same organs of interest (heartt and kidney)
- The impact of rescue strategies (senolytic drugs) to specifically target cellular senescence of tissular macrophages , mitigate inflammaging and improve cardiac and renal failure in the murine DOX-model of premature aging.