To examine the impact of combined loss of ZMAT3, PUMA and p21 in all tissues on the development of cancer, we aged Puma−/−p21−/−Zmat3−/− TKO as well as Puma−/−Zmat3−/−, p21−/−Zmat3−/− and as controls Trp53−/− as well as wt mice for 450–500 days. The gene discussed is TP53; the disease is cancer.