Sirt6 regulates lifespan in <i>Drosophila melanogaster</i>

Significance Sirt6 is well known for its role in regulating the aging process, particularly for its ability to extend lifespan in mice when overexpressed. However, the underlying molecular mechanisms responsible for lifespan regulation by Sirt6 are not well understood. Here, we characterized dSirt6 in fruit flies ( Drosophila melanogaster ). We found that dSirt6 functions very similarly to mammalian Sirt6 at the molecular and biochemical levels. Furthermore, overexpressing dSirt6 increased lifespan in flies. dSirt6 overexpression extends lifespan, in part, by opposing the activity of Myc, a master regulator of protein synthesis, which is associated with decreased protein synthesis. These findings have relevance for the treatment of age-related disease by modulating Sirt6 activity.