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Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8137-42. doi: 10.1073/pnas.1315461111. Epub 2014 May 12.

Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling.

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  • 1Program in Cellular and Molecular Biology.
  • 2Department of Molecular and Integrative Physiology.
  • 3Department of Molecular and Integrative Physiology,Medical Scientist Training Program, and.
  • 4Growth Control Unit, Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland; and.
  • 5Growth Control Unit, Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland; andDepartment of Biological Sciences, Wayne State University, Detroit, MI 48202.
  • 6Program in Cellular and Molecular Biology,Department of Molecular and Integrative Physiology,Geriatrics Center, University of Michigan, Ann Arbor, MI 48109;


Sensory perception modulates lifespan across taxa, presumably due to alterations in physiological homeostasis after central nervous system integration. The coordinating circuitry of this control, however, remains unknown. Here, we used the Drosophila melanogaster gustatory system to dissect one component of sensory regulation of aging. 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. This work provides an example of how discrete gustatory signals recruit nutrient-dependent endocrine systems to coordinate metabolic homeostasis, thereby influencing long-term health and aging.


adipokinetic hormone signaling; taste

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