Serotonin signaling modulates aging-associated metabolic network integrity in response to nutrient choice in Drosophila melanogaster

Abstract

Aging arises from complex interactions among multiple biochemical products. Systems-level analyses of biological networks may provide insights into the causes and consequences of aging that evade single-gene studies. We have previously found that dietary choice is sufficient to modulate aging in the vinegar fly, Drosophila melanogaster. Here we show that nutrient choice influenced several measures of metabolic network integrity, including connectivity, community structure, and robustness. Importantly, these effects are mediated by serotonin signaling, as a mutation in serotonin receptor 2A (5-HT2A) eliminated the effects of nutrient choice. Changes in network structure were associated with organism resilience and increased susceptibility to genetic perturbation. Our data suggest that the behavioral or perceptual consequences of exposure to individual macronutrients, involving serotonin signaling through 5-HT2A, qualitatively change the state of metabolic networks throughout the organism from one that is highly connected and robust to one that is fragmented, fragile, and vulnerable to perturbations.

G protein-coupled receptors that influence lifespan of human and animal models

“…Dietary options have been reported to reduce life expectancy in Drosophila , and the 5HT2a receptor is one of the main culprits due to its role in establishing the protein value of meals (Ro et al 2016 ). In this way, the interruption of their signaling eliminated the mortality differences between the two dietary environments and a change in the state of metabolic networks was observed throughout the organism from a fragmented, fragile and vulnerable to perturbations to a highly connected and robust one (Lyu et al 2021b , a ). Notably, experimental trials with Caenorhabditis found that mutations affecting the enzymes that regulate its biosynthesis and serotonin transporters produce small or modest effects on its lifespan.…”

Serotonergic Neurons in the Brain and Gnathal Ganglion of Larval Spodoptera frugiperda

“…Particularly, the modulation of serotonin on feeding-related processes has been intensively studied in several insect species, including locust, aphid ( Kaufmann et al, 2004 ), bugs ( Orchard, 2006 ), bees ( French et al, 2014 ), mosquitoes ( Novak and Rowley, 1994 ), and flies ( Haselton et al, 2009 ; Albin et al, 2015 ; Schoofs et al, 2018 ; Lyu et al, 2021 ). The serotonergic modulation is involved in feeding states, e.g., hunger and satiety and in a sequence of discrete events of feeding, such as, food detection, salivary secretion, food intake, and ingestion of food ( Tierney, 2020 ).…”