Tain, LS;
Sehlke, R;
Meilenbrock, RL;
Leech, T;
Paulitz, J;
Chokkalingam, M;
Nagaraj, N;
... Partridge, L; + view all
(2021)
Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila.
eLife
, 10
, Article e67275. 10.7554/eLife.67275.
Preview |
Text
Partridge_Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila_VoR.pdf - Published Version Download (1MB) | Preview |
Abstract
Reduced activity of the insulin/IGF signalling network increases health during ageing in multiple species. Diverse and tissue-specific mechanisms drive the health improvement. Here, we performed tissue-specific transcriptional and proteomic profiling of long-lived Drosophila dilp2-3,5 mutants, and identified tissue-specific regulation of >3600 transcripts and >3700 proteins. Most expression changes were regulated post-transcriptionally in the fat body, and only in mutants infected with the endosymbiotic bacteria, Wolbachia pipientis, which increases their lifespan. Bioinformatic analysis identified reduced co-translational ER targeting of secreted and membrane-associated proteins and increased DNA damage/repair response proteins. Accordingly, age-related DNA damage and genome instability were lower in fat body of the mutant, and overexpression of a minichromosome maintenance protein subunit extended lifespan. Proteins involved in carbohydrate metabolism showed altered expression in the mutant intestine, and gut-specific overexpression of a lysosomal mannosidase increased autophagy, gut homeostasis, and lifespan. These processes are candidates for combatting ageing-related decline in other organisms.
| Type: | Article |
|---|---|
| Title: | Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.67275 |
| Publisher version: | https://doi.org/10.7554/eLife.67275 |
| Language: | English |
| Additional information: | Copyright © 2021, Tain et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10127301 |
Archive Staff Only
 |
View Item |
