The two apparently divergent aspects of p53 function — pro-ageing and anti-ageing — are probably non-exclusive and relate to the activity levels of p53, the kinetics of its activation and the cellular or genetic context. Although deletion of p53 is able to reverse many of these cellular and organismal ageing phenotypes, the beneficial impact of p53 inactivation on ageing and stem cells is offset by the increased risk of cancer. These results highlight the need for an improved understanding of the circuitry of the p53-mediated checkpoint network, as such insights may provide avenues for improved management of the ageing consequences while suppressing the development of cancer. Along these lines, it is notable that deletion of p21Cip, a p53 target and a negative cell-cycle regulator, attenuates tissue degeneration in a number of organs in late-generation Terc−/− mice without increasing the risk of cancer65. Thus, further systematic dissection of the network of p53 may illuminate novel therapeutic avenues for the optimal management of ageing and cancer risks.
