Ketogenic diet induces p53-dependent cell senescence in multiple organs

Mice on two different ketogenic diets induce p53 and cellular senescence in multiple organs, including heart and kidney. This is mediated through inactivation of MDM2 by caspase-2 cleavage, leading to p53 accumulation and induction of p21. Ketogenic diet also induced pAMPK, suggesting that persistent activation leads to p53-dependent senescence. Mice were placed on ketogenic diet for three weeks. Their tissues (heart, kidney and liver) were collected (3 replicates each) and analyzed via immunoblotting and RNA-seq as compared to mice on a standard chow diet.