We note that the cellular response to p53 activation during this cycle of damage and response might be dependent on threshold concentrations of ROS. Under conditions of low oxidative stress, p53 activation preferentially induces expression of antioxidant genes; however, when ROS production is high, p53 instead activates pro-oxidant genes86. This contrasting action of p53 might allow either cell-cycle arrest and repair under conditions of modest DNA damage or more robust cellular responses of senescence or apoptosis and/or mitochondrial dysfunction in cells with more substantial DNA damage, thus leading to tissue atrophy and functional decline74.
