Figure 16. Understanding cell cycle arrest, senescence and autophagy: The sensescence-autophagy transition (SAT). Previously, we showed that recombinant expression of autophagy-associated genes (BNIP3, cathepsin B or ATG16L1) is sufficient to induce senescence, driving the autophagy-senescence transition (AST). Here, we show that recombinant expression of CDK inhibitors (p16/p19/p21) is sufficient to induce autophagy, driving the senescence-autophagy transition (SAT). Both SAT and AST result in mitochondrial dysfunction and a metabolic shift toward glycolysis, “powering down” cells during cell cycle arrest. Thus, cell cycle arrest, autophagy and senescence are all part of the same metabolic program that occurs in response to cellular stress.