As humans age, p53 mutations can accumulate in normal tissues. p53 functions as a transcription factor to drive cell-type dependent responses, such as apoptosis and cell cycle arrest. Recently, non-canonical functions of p53 have been proposed, such as suppression of repetitive elements including mobile elements. In this proposal, we will dissect mechanisms by which p53 regulates repetitive elements using in vitro techniques and in vivo mouse models. These studies will reveal novel functions of p53 that will not only provide insights into how p53 regulates mobile elements, but will also shed light on the impact of mobile element expression on the phenotypes of cells and organs. Ultimately, this knowledge will not only be useful for understanding p53 function, but will also provide insight into mechanisms of normal tissue aging.