a normal or extended lifespan (up to 16% longer), with delayed onset of the ageing phenotype, a result that has been attributed to lower ROS concentrations and ROS-related damage to proteins and lipids81. Further highlighting the complexity of p53 signalling, mice with a hypomorphic allele of Mdm2, the major negative regulator of p53, have not been reported to develop overt signs of premature ageing in the presence of enhanced p53 activity82. Finally, inactivation of p53 may not be sufficient to sustain viability in the setting of extremely severe telomere dysfunction and rampant chromosomal stability83,84.
