The serotonin receptor 5-HT2A modulates lifespan and protein feeding in Drosophila melanogaster

Abstract

The conserved neurotransmitter serotonin has been shown to be an important modulator of lifespan in specific nutritional contexts; however, it remained unclear how serotonin signaling influences lifespan under normal conditions. Here, we show that serotonin signaling through the 5-HT2A receptor influences lifespan, behavior, and physiology in Drosophila. Loss of the 5-HT2A receptor extends lifespan and induces a resistance to changes in dietary protein that are normally detrimental to lifespan. 5-HT2A−/− null mutant flies also display decreased protein feeding and protein content in the body. Therefore, serotonin signaling through receptor 5-HT2A is likely recruited to promote motivation for protein intake, and chronic reduction of protein-drive through loss of 5-HT2A signaling leads to a lower protein set-point adaptation, which influences physiology, decreases feeding, and increases lifespan. Our findings reveal insights into the mechanisms by which organisms physiologically adapt in response to perceived inability to satisfy demand.

Molecular correlates of swarming behaviour inAedes aegyptimales

“…In swarming males, upregulated genes included Pyruvate dehydrogenase phosphatase ( Pdp , AAEL025907-RA) that is involved in both metabolic and signalling pathways, Ephrin tyrosin kinase receptor ( Eph , AAEL010711-RD) whose product promotes cell adhesion and axon guidance, polybromo (AAEL000181-RF) encoding a chromatin remodeler, and serotonin receptor 2A ( 5-HT2A , AAEL019804-RF) implicated in food choice, ageing and modulation of circadian behaviour [23,36]. Additional genes of interest were slowpoke ( slo , AAEL018306-RF), whose product is a potassium ion channel (BK type) involved in odour recognition in Anopheles gambiae [37] and in the synchronisation of circadian neurons in flies [22], and Bardet-Bield syndrome 1 ( BBS1 , AAEL009211-RC) that encodes a protein expressed in sensory neurons in Drosophila , important for cilia biogenesis [38].…”

Constitutive and conditional epitope-tagging of endogenous G protein coupled receptors inDrosophila

“…5A-D) prompting us to review the influence of 5-HT2A on behavior and its potential relationship to specific anatomic structures. In the adult fly, loss of 5- HT2A leads to defects in feeding (Gasque et al, 2013; Munneke et al, 2022), increased lifespan (Munneke et al, 2022), and an altered response to the death of conspecifics (Chakraborty et al, 2019). The response to death has been linked to signaling in the EB, suggesting that 5-HT2A might be enriched at this site (Gendron et al, 2023).…”

Endocrine Regulation of Aging in the Fruit Fly Drosophila melanogaster

“…Not only the neuronal response to the dietary choice but also the downstream reprogramming of metabolic pathways, require 5-HT2A (Lyu et al, 2021). Similarly, under nutrient-replete conditions, 5-HT2A mutants exhibit decreased protein intake and prolonged lifespan (Munneke et al, 2022). Taken together, these findings indicate that blocking serotonin signaling abolishes protein sensibility and mimics the benefit of DR.…”