Global Epigenetic Changes and Derepression of Transposable Elements in Replicative Senescence

Aging is the main risk factor for most chronic diseases, disabilities, and declining health. It has long been proposed that senescent cells—damaged cells that have lost the ability to divide –drive the deterioration that underlies aging and agerelated diseases. However, definitive evidence for this relationship has been lacking. The use of a progeroid mouse model (which expresses low amounts of the mitotic checkpoint protein BubR1) has been instrumental in demonstrating that p16-positive senescent cells drive age-related pathologies and that selective elimination of these cells can prevent or delay age-related deterioration. Experiment designed to dissect how senescent cells develop in BubR1 progeroid mice and how they contribute to aging in this model will be presented. Senescent cells have become attractive therapeutic targets for the treatment of aging and age-related diseases. The potential applications and implications of such intervention strategies will be discussed.