Journal Article

Cell Non-Autonomous Activation of Flavin-containing Monooxygenase Promotes Longevity and Healthspan

Primitivo, Melissa, Ramos, Fresnida J., Kaeberlein, Matt, Miller, Hillary, Fletcher, Marissa, Leiser, Scott F., Rossner, Ryan, Leonard, Alison, Miller, Dana L., Rintala, Nicholas

2015

Overview

Stabilization of the hypoxia-inducible factor-1 (HIF-1) increases lifespan and healthspan in nematodes through an unknown mechanism. We report that neuronal stabilization of HIF-1 mediates these effects in C. elegans through a cell non-autonomous signal to the intestine resulting in activation of the xenobiotic detoxification enzyme flavin-containing monooxygenase-2 (FMO-2). This pro-longevity signal requires the serotonin biosynthetic enzyme TPH-1 in neurons and the serotonin receptor SER-7 in the intestine. Intestinal FMO-2 is also activated by dietary restriction (DR) and necessary for DR-mediated lifespan extension, suggesting that this enzyme represents a point of convergence for two distinct longevity pathways. FMOs are conserved in eukaryotes and induced by multiple lifespan-extending interventions in mice, suggesting that these enzymes may play a critical role in promoting health and longevity across phyla.