Sirtuin-1 Signaling Regulates Organismal Growth by Altering Feeding Behavior and Stem Cell Differentiation in Planarians.
Food consumption leads to an increase in body size in the planarian model Schmidtea mediterranea. How food consumption integrates with cell division at the organismal level remains unclear. Here we show that Sirtuin-1 signaling is evolutionarily conserved in planarians and specifically demonstrate that Sirtuin-1 (Smed-Sirt1) regulates growth by impairing both feeding behavior and stem cell differentiation. Disruption of Sirtuin-1 with either RNAi or pharmacological treatment leads to reduced animal growth. Conversely, activation of Sirtuin1 with resveratrol accelerates growth. Differences in growth rates were associated with changes in the amount of time to locate food and overall consumption. Furthermore, Smed-Sirt-1(RNAi) animals displayed reduced cell death and increased stem cell proliferation accompanied by impaired differentiation of intestinal lineage progenitors that resulted in reduced branching of the gut. Altogether, our findings indicate Sirtuin-1 signaling is a crucial metabolic hub capable of controlling animal behavior, tissue renewal and morphogenesis of the adult intestine.