Figure 2.

Senescent cell clearance via increasing p53 activity. Various situations, such as chemotherapy (Cisplatin, Taxol), radiation, replicative proliferation, and H-Ras overexpression, induce normal cells to undergo senescence. Activity of p53 is lower in most senescent cells than in normal cells. p53 forms a complex with Foxo4 or Mdm2, regulating p53 stabilization. Disruption of p53/Foxo4 or p53/Mdm2 interaction increases p53 activity in senescent cells through Foxo4-DRI or UBX0101 and P5091 treatment, respectively. Increasing p53 activity promotes senescent cell apoptosis.