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Journal Article

Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila

MPS-Authors
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Tain,  L.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons276060

Sehlke,  R.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Meilenbrock,  R. L.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Leech,  T.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons276066

Paulitz,  J.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129428

Grönke,  S.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons276068

Fröhlich,  J.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons104734

Atanassov,  Ilian
Proteomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129348

Partridge,  L.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/33879316
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Citation

Tain, L., Sehlke, R., Meilenbrock, R. L., Leech, T., Paulitz, J., Chokkalingam, M., et al. (2021). Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila. Elife, 10. doi:10.7554/eLife.67275.


Cite as: https://hdl.handle.net/21.11116/0000-000A-B7A3-F
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.