In mouse, not every antioxidant gene extends lifespan

We recently discussed evidence that the Drosophila gene Nrf2 is involved in antioxidant defense, cancer prevention and longevity assurance — at least in the fly. A new study by Pearson et al., however, suggests the system may be more complicated in mammals. In mice, it appears that the Nrf2 homolog is required for cancer prevention by calorie restriction (CR), but dispensable for the lifespan phenotype of CR.

Open questions: Outside of a CR paradigm, is mNrf2 involved in regulation of lifespan in ad libitum-fed animals? If not, has some other gene picked up Nrf2’s longevity-related functions, or is the role in lifespan determination an idiosyncrasy of the fly?