Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster
Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reducti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.893444/full |
| _version_ | 1797659129209159680 |
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| author | Nikolett Dravecz Tommy Shaw Isabella Davies Casey Brown Lewis Ormerod Gin Vu Tyler Walker Taran Taank Alan D. Shirras Susan J. Broughton |
| author_facet | Nikolett Dravecz Tommy Shaw Isabella Davies Casey Brown Lewis Ormerod Gin Vu Tyler Walker Taran Taank Alan D. Shirras Susan J. Broughton |
| author_sort | Nikolett Dravecz |
| collection | DOAJ |
| description | Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in Drosophila neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes. We hypothesize that individual neuronal subtypes respond differently to IIS changes, thus the behavioral outcomes of pan-neuronal IIS reduction are the balance of positive, negative and neutral functional effects. In order to further understand how reduced IIS in neurons independently modulates lifespan and locomotor behavioral senescence we expressed a dominant negative Insulin receptor transgene selectively in individual neuronal subtypes and measured the effects on lifespan and two measures of locomotor senescence, negative geotaxis and exploratory walking. IIS reduction in cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons was found to have either no affect or a detrimental effect on lifespan and locomotor senescence. However, reduction of IIS selectively in serotonergic neurons resulted in extension of lifespan in females with no effect on locomotor senescence. These data indicate that individual neuronal subtypes respond differently to IIS changes in the modulation of lifespan and locomotor senescence, and identify a specific role for the insulin receptor in serotonergic neurons in the modulation of lifespan. |
| first_indexed | 2024-03-11T18:10:23Z |
| format | Article |
| id | doaj.art-a407667128be4295a1359582ea0f8e7f |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-11T18:10:23Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-a407667128be4295a1359582ea0f8e7f2023-10-16T18:07:28ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-07-011410.3389/fnagi.2022.893444893444Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogasterNikolett DraveczTommy ShawIsabella DaviesCasey BrownLewis OrmerodGin VuTyler WalkerTaran TaankAlan D. ShirrasSusan J. BroughtonReduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in Drosophila neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes. We hypothesize that individual neuronal subtypes respond differently to IIS changes, thus the behavioral outcomes of pan-neuronal IIS reduction are the balance of positive, negative and neutral functional effects. In order to further understand how reduced IIS in neurons independently modulates lifespan and locomotor behavioral senescence we expressed a dominant negative Insulin receptor transgene selectively in individual neuronal subtypes and measured the effects on lifespan and two measures of locomotor senescence, negative geotaxis and exploratory walking. IIS reduction in cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons was found to have either no affect or a detrimental effect on lifespan and locomotor senescence. However, reduction of IIS selectively in serotonergic neurons resulted in extension of lifespan in females with no effect on locomotor senescence. These data indicate that individual neuronal subtypes respond differently to IIS changes in the modulation of lifespan and locomotor senescence, and identify a specific role for the insulin receptor in serotonergic neurons in the modulation of lifespan.https://www.frontiersin.org/articles/10.3389/fnagi.2022.893444/fullageingbehavioral senescenceinsulin/IGF-like signalingserotonergic neuronsDrosophila |
| spellingShingle | Nikolett Dravecz Tommy Shaw Isabella Davies Casey Brown Lewis Ormerod Gin Vu Tyler Walker Taran Taank Alan D. Shirras Susan J. Broughton Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster Frontiers in Aging Neuroscience ageing behavioral senescence insulin/IGF-like signaling serotonergic neurons Drosophila |
| title | Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster |
| title_full | Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster |
| title_fullStr | Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster |
| title_full_unstemmed | Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster |
| title_short | Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster |
| title_sort | reduced insulin signaling targeted to serotonergic neurons but not other neuronal subtypes extends lifespan in drosophila melanogaster |
| topic | ageing behavioral senescence insulin/IGF-like signaling serotonergic neurons Drosophila |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.893444/full |
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