Positive and negative gustatory inputs affect Drosophila lifespan partly in parallel to dFOXO signaling

Abstract

In Caenorhabditis elegans, a subset of gustatory neurons, as well as olfactory neurons, shortens lifespan, whereas a different subset of gustatory neurons lengthens it. Recently, the lifespan-shortening effect of olfactory neurons has been reported to be conserved in Drosophila. Here we show that the Drosophila gustatory system also affects lifespan in a bidirectional manner. We find that taste inputs shorten lifespan through inhibition of the insulin pathway effector dFOXO, whereas other taste inputs lengthen lifespan in parallel to this pathway. We also note that the gustatory influence on lifespan does not necessarily depend on food intake levels. Finally, we identify the nature of some of the taste inputs that could shorten versus lengthen lifespan. Together our data suggest that different gustatory cues can modulate the activities of distinct signaling pathways, including different insulin-like peptides, to promote physiological changes that ultimately affect lifespan.sensory system | insulin signaling | physiology | gustatory receptors | aging A ging is a universal process that causes deterioration in the biological functions of an organism over the progression of its lifetime. This process is affected by genetic and environmental factors, whose interaction could be mediated by the sensory system, which perceives and transmits environmental information to modulate the signaling activities of downstream target tissues. Accordingly, external sensory cues and sensory neuron activities have been shown to alter the lifespan of both Caenorhabditis elegans and Drosophila melanogaster (1-6).In C. elegans, the laser ablation of a specific subset of gustatory or olfactory neurons extends lifespan, whereas ablation of a different subset of gustatory neurons shortens it (1). Interestingly, at least part of this sensory influence on lifespan has also been observed in other animals. In Drosophila, impairment of olfaction through a mutation in Or83b, which encodes a broadly expressed atypical odorant receptor (7), increases lifespan (3). In addition, exposure of dietary-restricted flies to food odors, like live yeast, can partly suppress their long-life phenotype (3). The conservation of the olfactory influence on lifespan is thus consistent with the possibility that gustatory inputs will also bidirectionally alter the lifespan of both C. elegans and D. melanogaster.The effects of sensory neurons on C. elegans lifespan have been shown to be partly mediated by insulin/IGF signaling (1, 2, 8). The insulin/IGF pathway also affects fly lifespan: down-regulation of the activities of the insulin receptor InR and the receptor substrate, CHICO, extends lifespan (9, 10). Moreover, an increase in activity of the downstream transcription factor dFOXO, which is negatively regulated by both InR and CHICO, increases fly lifespan (11,12). Consistent with these observations, mutations in several of the Drosophila insulin-like peptide (dilp) genes (13), which are expressed in the median neurosecretory cells (mNSCs) in the fly brain (14-1...

Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling

“…Previous work has provided compelling evidence that nutrientsensing signaling pathways are key regulators of longevity (10,43). Additionally, there is a conserved role for the function of chemosensory systems in control of aging (1,5,6,44,45), including a study in PNAS showing that subsets of gustatory inputs were capable of modulating Drosophila lifespan in a bidirectional manner (6). One logical prediction followed that, in response to transduction and integration of a taste signal, an organism reprograms its metabolic state through modulation of nutrient homeostatic pathways, ultimately altering lifespan.…”

Chemical activation of a food deprivation signal extends lifespan

“…Sensory systems that detect environmental stimulus mediate at least part of this influence on lifespan. In the nematode C. elegans, as well as in D. melanogaster, the removal of sensory neurons can modulate the lifespan of the organism (Apfeld & Kenyon, 1999; Alcedo & Kenyon, 2004; Libert et al ., 2007; Poon et al ., 2010; Ostojic et al ., 2014). Recent work has also shown that sensory signaling can also modulate the lifespan of vertebrates (Riera et al ., 2014).…”

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides

“…Gustatory and olfactory neurons, which perceive chemical signals, are some of the sensory neurons that have been shown to affect life span (Alcedo and Kenyon 2004;Libert et al 2007;Poon et al 2010;Ostojic et al 2014;Waterson et al 2014). In C. elegans, chemosensory neuronal signaling is initiated by the binding of chemical ligands to sensory G protein-coupled receptors (GPCRs), which in turn activates G protein signaling cascades to transduce the signals that increase cyclic GMP (cGMP) levels (Bargmann 2006).…”