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

Tain, L. S., 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: e67275. doi:10.7554/eLife.67275.

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Genre: Journal Article

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https://elifesciences.org/articles/67275 (Publisher version)
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Open Access

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 Creators:
Tain, Luke Stephen1, Author
Sehlke, Robert1, Author
Meilenbrock, Ralf Leslie1, Author
Leech, Thomas1, Author
Paulitz, Jonathan1, Author
Chokkalingam, Manopriya1, Author
Nagaraj, Nagarjuna2, Author              
Groenke, Sebastian1, Author
Froehlich, Jenny1, Author
Atanassov, Ilian1, Author
Mann, Matthias2, Author              
Beyer, Andreas1, Author
Partridge, Linda1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: MESSENGER-RNA TRANSLATION; EXTENDS LIFE-SPAN; DNA-DAMAGE; DIETARY RESTRICTION; CELLULAR-RESPONSE; OXIDATIVE STRESS; MCM PROTEINS; STEM-CELLS; LONGEVITY; PROTEOSTASISLife Sciences & Biomedicine - Other Topics;
 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.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published online
 Pages: 30
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000643549900001
DOI: 10.7554/eLife.67275
 Degree: -

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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 10 Sequence Number: e67275 Start / End Page: - Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X