Gustatory Regulation of Physiology and Longevity in Drosophila melanogaster.

[摘要] Chemosensory perception is critical for the assessment of an organism’s nutritive environment, allowing for an appropriate physiological response to a given set of chemical stimuli.Its broad perturbations in model organisms regulate lifespan.A detailed understanding of the underlying circuitry which coordinated this control, though, remained largely unknown.Here, we utilized the gustatory system of Drosophila melanogaster as a model to study this regulation, finding that loss of function of individual gustatory genes caused significant, bidirectional alterations in lifespan. We focused on two inputs – the long-lived ppk28 water-sensing mutants and short-lived Gr5a sweet receptor mutants – to determine the underlying longevity-regulating mechanisms. In ppk28 mutants, we found substantial augmentation of nutrient stores. We determined that the glucagon-like adipokinetic hormone [AKH] was specifically upregulated and required for increased longevity, as was the transcription factor dFoxO.Importantly, we demonstrated ppk28 mutants adaptively respond to lack of water gustatory information via AKH upregulation, altering nutrient metabolism to promote a physiological state conducive to both the production of metabolic water and increased longevity. In Gr5a mutants, we found that both whole-organism and hemolymph levels of selectively trehalose – the ligand for the Gr5a receptor – were increased. We propose that this increase is due to upregulation of de novo trehalose synthesis, and present evidence suggesting that Gr5a mutants respond to augmented hemolymph trehalose levels via increasing action of insulin-like peptide signaling, a modulation congruous with a short-lived phenotype.These studies uncovered, in the greatest detail yet attained, how discrete gustatory information regulates Drosophila lifespan through the modulation of CNS-derived endocrine molecules responsible for control of nutrient homeostasis.The resultant metabolic switches which occur from the transduction of taste information through this circuitry, in turn, determined health and lifespan status of the organism. They also suggest that loss of the ability to sense a metabolically important molecule is sufficient to induce metabolism toward generating increased internal amounts. This work is thus important for both the understanding of the basic biology of sensory signaling and how this signaling is capable of regulating – and may be targeted to increase – organismal long-term health and lifespan.

[发布机构] University of Michigan

[效力级别] Aging

[关键词] Taste Perception;Aging;Physiology;Science;Cellular & Molecular Biology