P53 and aging: A fresh look at an old paradigm

Apoptosis and cellular senescence, two key tumor suppression mechanisms, are thought to be antagonistically pleiotropic.Antagonistic pleiotropy holds that functions that are advantageous for a young and reproductively fit organism (eg.cancer protection and proper development) can be deleterious when that same organism becomes old (eg.loss of stem cell proliferation and tissue degeneration leading to diseases associated with age) [1].This theory predicts that in an older animal (or human), the activity of tumor suppressors would be associated with enhanced aging phenotypes.However, confirmation of a direct connection between apoptosis, senescence and aging remains elusive [2].In fact, at least in the case of p53 there is mounting data challenging the antagonistic pleiotropy model.