You might recall that p66(Shc) mice are long-lived for reasons that are still open for debate - they are a good illustration of the sheer complexity of attempting to safely extend life through metabolic manipulation, and the time taken to understand what is going on. Here is more on the subject: "Evidence is mounting that reactive oxygen species (ROS) produced because of stressful challenges could interfere with the proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in greater vulnerability to aging and neurodegeneration. Here we tested the hypothesis that p66(Shc-/-) mice, which have been described to have an extended life span and a high resistance to oxidative stress, might be less susceptible to the effects of inflammatory insults at adulthood. ... Overall, the greater resilience to inflammation-induced changes in the p66(Shc-/-) mutants might underlie the better health status and the greater longevity characterizing these mice." Chronic inflammation that increases with age - due to putting on visceral fat, or increasing disorder in the immune system - is a big issue. Protection against it is similarly important.