Editors' ChoicePhysiology

Aging: All in the head—and the gut

Sci. Signal.  15 Dec 2015:
Vol. 8, Issue 407, pp. ec374
DOI: 10.1126/scisignal.aae0540

The effects of hypoxia and caloric restriction, both of which extend life span in Caenorhabditis elegans, converge on the activation of an enzyme in cells of the intestine. Leiser et al. show that the life-extending effects of hypoxia begin in neurons with transcriptional activation by hypoxia-inducible factor–1 and increased serotonergic signaling. These effects lead to increased production of flavin-containing monooxygenase-2 (FMO-2) in the intestine, which increased longevity. Finding the relevant targets of FMO-2, which also accumulates in mammals under conditions that promote longevity, may elucidate further mechanisms that promote healthy aging.

S. F. Leiser, H. Miller, R. Rossner, M. Fletcher, A. Leonard, M. Primitivo, N. Rintala, F. J. Ramos, D. L. Miller, M. Kaeberlein, Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span. Science 350, 1375–1378 (2015). [Abstract] [Full Text]