title: Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling.
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.
authors.affiliation: Program in Cellular and Molecular Biology.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Waterson
authors.affiliation: Department of Molecular and Integrative Physiology.
authors.forename: Brian Y
authors.initials: BY
authors.lastname: Chung
authors.affiliation: Department of Molecular and Integrative Physiology,Medical Scientist Training Program, and.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Harvanek
authors.affiliation: Growth Control Unit, Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland; and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ostojic
authors.affiliation: Growth Control Unit, Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland; andDepartment of Biological Sciences, Wayne State University, Detroit, MI 48202.
authors.forename: Joy
authors.initials: J
authors.lastname: Alcedo
authors.affiliation: Program in Cellular and Molecular Biology,Department of Molecular and Integrative Physiology,Geriatrics Center, University of Michigan, Ann Arbor, MI 48109; spletch@umich.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Pletcher
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism* / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D005502:Food; D006706:Homeostasis / Q000502:physiology; D007301:Insect Hormones / Q000378:metabolism*; D008136:Longevity / Q000502:physiology; D008297:Male; D055099:Neuroendocrine Cells / Q000378:metabolism / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013649:Taste / Q000502:physiology*; D014867:Water / Q000378:metabolism
chemical_list: C533337:AKHR protein, Drosophila; D029721:Drosophila Proteins; D053503:Epithelial Sodium Channels; D007301:Insect Hormones; D009842:Oligopeptides; C549272:PPK28 protein, Drosophila; D018027:Receptors, Glucagon; C044833:adipokinetic hormone; D014867:Water; C065368:DAKH peptide; D011761:Pyrrolidonecarboxylic Acid
keywords: adipokinetic hormone signaling; taste