The single gene mutations and targeted antioxidant methodologies for increased longevity are rolling in of late. I expect that the optimization of mouse metabolism will accelerate as the biotechnology revolution continues to pick up speed - that, sadly, is still the goal most research groups are aiming for, rather than identification and repair of age-related damage. Still, at this rate, the existing Mprize champions will be dethroned by the end of 2012.
Here's the most recent example, coming out of focused research into one small part of the grand complexity of mammalian biochemistry:
Genetic deletion in mice of pregnancy-associated plasma protein A (PAPP-A), a recently identified metalloproteinase in the insulin-like growth factor system, extends by 30-40% both mean and maximum lifespan with no reduction in food intake or secondary endocrine abnormalities. Furthermore, these mice have markedly reduced incidence of spontaneous tumors. The findings implicate PAPP-A as a critical regulator of lifespan and age-related diseases, and suggest PAPP-A as a possible target to promote longevity.
More life, less cancer, no obvious downside - for mice, in any case. It is interesting to note that these divergent genetic engineering and other methodologies for tweaking metabolic processes seem to top out at around 30-40% increased longevity in mice, just like calorie restriction. That does tend to suggest a commonality of mechanisms at the base of it all.