Exploring the effect of redox enzyme modulation on the biology of mouse aging

The oxidative stress theory of aging has been the most studied and tested mechanistic theory of why organisms age. However, most recent data on this theory suggest that broadly altering levels of oxidative stress or accumulation of oxidative damage has limited effects on the regulation of lifespan in mammals. This has led to the proposition that aging may be regulated through oxidation-induced changes to cellular redox state and redox signaling rather than through general oxidative stress mechanisms. Redox regulation of cell survival and homeostasis through modulating the pathways necessary for gene regulation, protein activation and deactivation, and apoptosis might then amplify minor alterations in oxidative stress to have drastic effects on an organism. In this chapter, we discuss the evidence that alterations in cellular redox state are associated with mammalian aging and discuss the mouse models available to test whether redox regulation is a significant factor in the aging process. In general, these data suggest that mammalian aging may be regulated in part by cellular redox state and support further investigation to address whether modulation of redox state can significantly alter lifespan and healthspan.