You may recall that SIRT1 is a major player in the mechanisms by which calorie restriction extends healthy life span. However, as reported at EurekAlert, "we showed that, unlike in yeast, mouse SIRT1 can function to suppress cellular longevity rather than to promote it. That has been a big surprise to the field since it does not fit with preconceived notions of the role of SIRT1 ... SIRT1 affects a particular response pathway to DNA-damaging oxidation. They found that SIRT1-deficient cells, in contrast to normal cells, continued to divide when treated chronically with low-level doses of oxidation-inducing hydrogen peroxide. However, the SIRT1-deficient cells had a normal senescence response when exposed to high-level oxidation or the activated cancer gene, Ras. Together, these results indicate that SIRT1 has a specific role in the response to chronic oxidative damage." More research is called for.