Gene targeting of SIRT1, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7 has been reported. The phenotypes include a reduction in median lifespan, ranging from a usual survival of days (SIRT1) to weeks (SIRT6) or months (SIRT7). In contrast, although biochemical phenotypes have been reported, Sirt3−/− and Sirt4−/− mice appear outwardly normal. Initial reports suggest that Sirt5−/− mice also exhibit no obvious phenotype.