It is well known that calorie restriction extends life in near all species in which it has been tested. In mammals much of this effect seems to operate through sensing low levels of methionine, an essential amino acid. Here researchers show that in flies in addition to mechanisms that react to the level of food intake there is a also water sensor that separately and distinctly alters metabolism so as to extend healthy life:
Sensory inputs are known to control aging. The underlying circuitry through which these cues are integrated into regulatory physiological outputs, however, remains largely unknown. Here, we use the taste sensory system of the fruit fly Drosophila melanogaster to detail one such circuit. Specifically, we find that water-sensing taste signals alter nutrient homeostasis and regulate a glucagon-like signaling pathway to govern production of internal water production. This metabolic alteration likely serves as a response to water sensory information. This control of metabolic state, in turn, determines the organism's long-term health and lifespan.
We found that loss of the critical water sensor, pickpocket 28 (ppk28), altered metabolic homeostasis to promote internal lipid and water stores and extended healthy lifespan. Additionally, loss of ppk28 increased neuronal glucagon-like adipokinetic hormone (AKH) signaling, and the AKH receptor was necessary for ppk28 mutant effects. Furthermore, activation of AKH-producing cells alone was sufficient to enhance longevity, suggesting that a perceived lack of water availability triggers a metabolic shift that promotes the production of metabolic water and increases lifespan via AKH signaling.