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Sirtuin-1 regulates organismal growth by altering feeding behavior and intestinal morphology in planarians

ABSTRACT Nutrient availability upon feeding leads to an increase in body size in the planarian Schmidtea mediterranea. However, it remains unclear how food consumption integrates with cell division at the organismal level. Here, we show that the NAD-dependent protein deacetylases sirtuins are evolutionarily conserved in planarians, and specifically demonstrate that the homolog of human sirtuin-1 (SIRT1) (encoded by Smed-Sirt-1), regulates organismal growth by impairing both feeding behavior and intestinal morphology. Disruption of Smed-Sirt-1 with RNAi or pharmacological inhibition of Sirtuin-1 leads to reduced animal growth. Conversely, enhancement of Sirtuin-1 activity with resveratrol accelerates growth. Differences in growth rates were associated with changes in the amount of time taken to locate food and overall food consumption. Furthermore, Smed-Sirt-1(RNAi) animals displayed reduced cell death and increased stem cell proliferation accompanied by impaired expression of intestinal lineage progenitors and reduced branching of the gut. Taken together, our findings indicate that Sirtuin-1 is a crucial metabolic hub capable of controlling animal behavior, tissue renewal and morphogenesis of the adult intestine. Summary: Sirtuins regulate organismal growth in planarians by altering animal behavior and disrupting the differentiation of cellular progenitors.