Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling

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

Abstract

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.

Keywords: adipokinetic hormone signaling; taste.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / physiology
  • Epithelial Sodium Channels / metabolism*
  • Female
  • Food
  • Homeostasis / physiology
  • Insect Hormones / metabolism*
  • Longevity / physiology
  • Male
  • Neuroendocrine Cells / metabolism
  • Neuroendocrine Cells / physiology
  • Oligopeptides / metabolism*
  • Pyrrolidonecarboxylic Acid / analogs & derivatives*
  • Pyrrolidonecarboxylic Acid / metabolism
  • Receptors, Glucagon / metabolism*
  • Signal Transduction / physiology*
  • Taste / physiology*
  • Water / metabolism

Substances

  • AKHR protein, Drosophila
  • Drosophila Proteins
  • Epithelial Sodium Channels
  • Insect Hormones
  • Oligopeptides
  • PPK28 protein, Drosophila
  • Receptors, Glucagon
  • adipokinetic hormone
  • Water
  • DAKH peptide
  • Pyrrolidonecarboxylic Acid