Xiangli Yang. Sirt1 is a NAD+-dependent protein deacetylase and a mammalian homologue of SIR2, a Caenorhabditis elegans gene can be extend life span when it is overexpressed. Our preliminary studies show that deletion of Sirt1 in mouse genome leads to severe osteopenic phenotypes. However, the molecular mechanisms by what cause the severe low bone mass in these mutant mice is under active investigation by several investigators of the center. Since Sirt1-deficient mice and Atf4-deficient mice show several striking phenotypes, including smaller statues, severe low bone mass, decreased bone formation rate, decreased osteoblast activities, and decreased osteoclast numbers and activities. Interestingly, we found that Sirt1 mRNA is upregulated in the Atf4-/- bones and many other tissues. This observation suggests a compensatory mechanism in which Sirt1 acts downstream of ATF4 to control osteoblast differentiation and activity. In the further studies, we plan to investigate whether Sirt1 activity is changed in the wildtype (wt) and Atf4-/- bones or osteoblasts. If it is the case, we will further study what are the causes for this changed Sirt1 activity.