The Drosophila insulin receptor independently modulates lifespan and locomotor senescence.
The Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence. To investigate...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0125312 |
| _version_ | 1818588806199115776 |
|---|---|
| author | Mohd Zamri Bin Haji Ismail Matt D Hodges Michael Boylan Rajesh Achall Alan Shirras Susan J Broughton |
| author_facet | Mohd Zamri Bin Haji Ismail Matt D Hodges Michael Boylan Rajesh Achall Alan Shirras Susan J Broughton |
| author_sort | Mohd Zamri Bin Haji Ismail |
| collection | DOAJ |
| description | The Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence. To investigate this role in Drosophila melanogaster, we measured the effect of reduced IIS on senescence of two locomotor behaviours, negative geotaxis and exploratory walking. Two long-lived fly models with systemic IIS reductions (daGAL4/UAS-InRDN (ubiquitous expression of a dominant negative insulin receptor) and d2GAL/UAS-rpr (ablation of insulin-like peptide producing cells)) showed an amelioration of negative geotaxis senescence similar to that previously reported for the long-lived IIS mutant chico. In contrast, exploratory walking in daGAL4/UAS-InRDN and d2GAL/UAS-rpr flies declined with age similarly to controls. To determine the contribution of IIS in the nervous system to these altered senescence patterns and lifespan, the InRDN was targeted to neurons (elavGAL4/UAS-InRDN), which resulted in extension of lifespan in females, normal negative geotaxis senescence in males and females, and detrimental effects on age-specific exploratory walking behaviour in males and females. These data indicate that the Drosophila insulin receptor independently modulates lifespan and age-specific function of different types of locomotor behaviour. The data suggest that ameliorated negative geotaxis senescence of long-lived flies with systemic IIS reductions is due to ageing related effects of reduced IIS outside the nervous system. The lifespan extension and coincident detrimental or neutral effects on locomotor function with a neuron specific reduction (elavGAL4/UAS-InRDN) indicates that reduced IIS is not beneficial to the neural circuitry underlying the behaviours despite increasing lifespan. |
| first_indexed | 2024-12-16T09:30:36Z |
| format | Article |
| id | doaj.art-f10239b8d3ee432eb30068169519727b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T09:30:36Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f10239b8d3ee432eb30068169519727b2022-12-21T22:36:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012531210.1371/journal.pone.0125312The Drosophila insulin receptor independently modulates lifespan and locomotor senescence.Mohd Zamri Bin Haji IsmailMatt D HodgesMichael BoylanRajesh AchallAlan ShirrasSusan J BroughtonThe Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence. To investigate this role in Drosophila melanogaster, we measured the effect of reduced IIS on senescence of two locomotor behaviours, negative geotaxis and exploratory walking. Two long-lived fly models with systemic IIS reductions (daGAL4/UAS-InRDN (ubiquitous expression of a dominant negative insulin receptor) and d2GAL/UAS-rpr (ablation of insulin-like peptide producing cells)) showed an amelioration of negative geotaxis senescence similar to that previously reported for the long-lived IIS mutant chico. In contrast, exploratory walking in daGAL4/UAS-InRDN and d2GAL/UAS-rpr flies declined with age similarly to controls. To determine the contribution of IIS in the nervous system to these altered senescence patterns and lifespan, the InRDN was targeted to neurons (elavGAL4/UAS-InRDN), which resulted in extension of lifespan in females, normal negative geotaxis senescence in males and females, and detrimental effects on age-specific exploratory walking behaviour in males and females. These data indicate that the Drosophila insulin receptor independently modulates lifespan and age-specific function of different types of locomotor behaviour. The data suggest that ameliorated negative geotaxis senescence of long-lived flies with systemic IIS reductions is due to ageing related effects of reduced IIS outside the nervous system. The lifespan extension and coincident detrimental or neutral effects on locomotor function with a neuron specific reduction (elavGAL4/UAS-InRDN) indicates that reduced IIS is not beneficial to the neural circuitry underlying the behaviours despite increasing lifespan.https://doi.org/10.1371/journal.pone.0125312 |
| spellingShingle | Mohd Zamri Bin Haji Ismail Matt D Hodges Michael Boylan Rajesh Achall Alan Shirras Susan J Broughton The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. PLoS ONE |
| title | The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. |
| title_full | The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. |
| title_fullStr | The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. |
| title_full_unstemmed | The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. |
| title_short | The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. |
| title_sort | drosophila insulin receptor independently modulates lifespan and locomotor senescence |
| url | https://doi.org/10.1371/journal.pone.0125312 |
| work_keys_str_mv | AT mohdzamribinhajiismail thedrosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT mattdhodges thedrosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT michaelboylan thedrosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT rajeshachall thedrosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT alanshirras thedrosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT susanjbroughton thedrosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT mohdzamribinhajiismail drosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT mattdhodges drosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT michaelboylan drosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT rajeshachall drosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT alanshirras drosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence AT susanjbroughton drosophilainsulinreceptorindependentlymodulateslifespanandlocomotorsenescence |