“…The activation of p53 occurs through multiple and complex mechanisms that include stabilization against proteolytic degradation and association to other proteins (reviewed in Prives, 1998;Giaccia and Kastan, 1998). In senescent human ®broblasts, the total levels of p53 do not change but its activity increases, as revealed by p53-speci®c assays for DNA binding and transcriptional activation (Rittling et al, 1986;Afshari et al, 1993;Atadja et al, 1995;Bond et al, 1996). Loss of functional p53 allows an extension of the proliferative potential of human ®broblasts in culture (Rogan et al, 1995;Bond et al, 1995;Medclaf et al, 1996;Yan et al, 1996;Gallimore et al, 1997;Gire and Wynford-Thomas, 1998).…”