Tain, Luke Stephen, Sehlke, Robert, Meilenbrock, Ralf Leslie, Leech, Thomas, Paulitz, Jonathan, Chokkalingam, Manopriya, Nagaraj, Nagarjuna, Groenke, Sebastian, Froehlich, Jenny, Atanassov, Ilian ORCID: 0000-0001-8259-2545, Mann, Matthias, Beyer, Andreas and Partridge, Linda (2021). Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila. eLife, 10. CAMBRIDGE: eLIFE SCIENCES PUBL LTD. ISSN 2050-084X

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tain, Luke StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sehlke, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meilenbrock, Ralf LeslieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leech, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paulitz, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chokkalingam, ManopriyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagaraj, NagarjunaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Groenke, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froehlich, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Atanassov, IlianUNSPECIFIEDorcid.org/0000-0001-8259-2545UNSPECIFIED
Mann, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Partridge, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-587782
DOI: 10.7554/eLife.67275
Journal or Publication Title: eLife
Volume: 10
Date: 2021
Publisher: eLIFE SCIENCES PUBL LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MESSENGER-RNA TRANSLATION; EXTENDS LIFE-SPAN; DNA-DAMAGE; DIETARY RESTRICTION; CELLULAR-RESPONSE; OXIDATIVE STRESS; MCM PROTEINS; STEM-CELLS; LONGEVITY; PROTEOSTASISMultiple languages
BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58778

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