p53 and Mouse Aging Models

This chapter discusses various mouse models of aging, with a particular emphasis on the potential role of p53 gene in regulating cellular senescence and organismal aging. A primary function of p53 is to protect the normal dividing cells from stress-induced damage. In an unstressed cell, p53 exists at low basal levels in the cytoplasm and is activated by a number of cellular insults, including DNA damage, hypoxia, and aberrant growth signaling. Posttranslational modifications play an important role in activating p53. There are many sites of phosphorylation and acetylation on p53. Many of these phosphorylations can occur rapidly following DNA damage. The ability of p53 to induce transient cell cycle arrest, apoptosis, and/or senescence in response to cellular stress is crucial for the prevention of tumorigenesis. In contrast to transient cell cycle arrest and apoptosis that allow for the repair and removal of damaged cells from tissues, respectively, senescence does not remove cells. Thus, cells that are dysfunctional or potentially neoplastic may be permanently retained. Posttranslational modifications of the p53 protein are critical for its stabilization and activation in response to cellular stressors. Both the phosphorylation and acetylation of p53 appear to play an important role in its ability to mediate the induction of cellular senescence.