Dietary restriction (DR) slows aging in many animals, while in some cases, the sensory signals from diet alone are sufficient to retard or accelerate lifespan. The digestive tract is a candidate location to sense nutrients, where neuropeptides secreted by enteroendocrine cells (EEC) produce systemic signals in response to food. Here, we measure how Drosophila neuropeptide F (NPF) is secreted into adult circulation by EEC and find that specific EEC differentially respond to dietary sugar and yeast. Female lifespan is increased when gut NPF is genetically depleted, and this manipulation is sufficient to blunt the longevity benefit conferred by DR. Depletion of NPF receptors at insulin-producing neurons of the brain also increases female lifespan, consistent with observations where loss of gut NPF decreases neuronal insulin secretion. The longevity conferred by repressing gut NPF and brain NPF receptors is reversed by treating adults with a juvenile hormone (JH) analog. JH is produced by the adult corpora allata, and inhibition of the insulin receptor at this tissue decreases JH titer and extends lifespan in both males and females, while this longevity is restored to wild type by treating adults with a JH analog. Overall, EEC of the gut modulate Drosophila aging through interorgan communication mediated by a gut-brain-corpora allata axis, and insulin produced in the brain impacts lifespan through its control of JH titer. These data suggest that we consider how human incretins and their analogs, which are used to treat obesity and diabetes, may impact aging.

• Klíčová slova
• aging, incretin, insulin, interorgan communication, juvenile hormone,
• MeSH
• dlouhověkost fyziologie   MeSH
• Drosophila melanogaster metabolismus   MeSH
• enteroendokrinní buňky metabolismus   MeSH
• inzulin * metabolismus   MeSH
• juvenilní hormony * metabolismus   MeSH
• mozek metabolismus   MeSH
• neurony metabolismus   MeSH
• neuropeptidy * metabolismus   MeSH
• osa mozek-střevo * fyziologie   MeSH
• proteiny Drosophily * metabolismus   genetika   MeSH
• stárnutí metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inzulin * MeSH
• juvenilní hormony * MeSH
• neuropeptide F, Drosophila MeSH Prohlížeč
• neuropeptidy * MeSH
• proteiny Drosophily * MeSH

Dietary restriction slows aging in many animals, while in some cases the sensory signals from diet alone are sufficient to retard or accelerate lifespan. The digestive tract is a candidate location to sense nutrients, where neuropeptides secreted by enteroendocrine cells (EEC) produce systemic signals in response to food. Here we measure how Drosophila neuropeptide F (NPF) is secreted into adult circulation by enteroendocrine cells and find that specific enteroendocrine cells differentially respond to dietary sugar and yeast. Lifespan is increased when gut NPF is genetically depleted, and this manipulation is sufficient to blunt the longevity benefit conferred by dietary restriction. Depletion of NPF receptors at insulin producing neurons of the brain also increases lifespan, consistent with observations where loss of gut NPF decreases neuronal insulin secretion. The longevity conferred by repressing gut NPF and brain NPF receptors is reversed by treating adults with a juvenile hormone (JH) analog. JH is produced by the adult corpora allata, and inhibition of the insulin receptor at this tissue decreases JH titer and extends lifespan, while this longevity is restored to wild type by treating adults with a JH analog. Overall, enteroendocrine cells of the gut modulate Drosophila aging through interorgan communication mediated by a gut-brain-corpora allata axis, and insulin produced in the brain impacts lifespan through its control of JH titer. These data suggest that we should consider how human incretins and their analogs, which are used to treat obesity and diabetes, may impact aging.

• Klíčová slova
• PYY, aging, incretins, insulin, interorgan communication, juvenile hormone,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

The rigorous balance of endocrine signals that control insect reproductive physiology is crucial for the success of egg production. Rhodnius prolixus, a blood-feeding insect and main vector of Chagas disease, has been used over the last century as a model to unravel aspects of insect metabolism and physiology. Our recent work has shown that nutrition, insulin signaling, and two main types of insect lipophilic hormones, juvenile hormone (JH) and ecdysteroids, are essential for successful reproduction in R. prolixus; however, the interplay behind these endocrine signals has not been established. We used a combination of hormone treatments, gene expression analyses, hormone measurements, and ex vivo experiments using the corpus allatum or the ovary, to investigate how the interaction of these endocrine signals might define the hormone environment for egg production. The results show that after a blood meal, circulating JH levels increase, a process mainly driven through insulin and allatoregulatory neuropeptides. In turn, JH feeds back to provide some control over its own biosynthesis by regulating the expression of critical biosynthetic enzymes in the corpus allatum. Interestingly, insulin also stimulates the synthesis and release of ecdysteroids from the ovary. This study highlights the complex network of endocrine signals that, together, coordinate a successful reproductive cycle.

• Klíčová slova
• corpus allatum, endocrine signaling, hormone titers, insect, ovary,
• MeSH
• ekdysteroidy metabolismus   MeSH
• hmyzí hormony * metabolismus   MeSH
• inzulin lidský MeSH
• inzulin metabolismus   MeSH
• juvenilní hormony metabolismus   MeSH
• Rhodnius * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ekdysteroidy MeSH
• hmyzí hormony * MeSH
• inzulin lidský MeSH
• inzulin MeSH
• juvenilní hormony MeSH