Tain, L.S., Sehlke, R., Meilenbrock, R.L., Leech, T., Paulitz, J., Chokkalingam, M., Nagaraj, N., Grönke, S., Fröhlich, J., Atanassov, I., Mann, M., Beyer, A., Partridge, L. (2021). Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila. eLife 10(): e67275.
FlyBase ID
FBrf0248748
Publication Type
Research paper
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.
