Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila
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Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila. / Tain, Luke Stephen; Sehlke, Robert; Meilenbrock, Ralf Leslie; Leech, Thomas; Paulitz, Jonathan; Chokkalingam, Manopriya; Nagaraj, Nagarjuna; Grönke, Sebastian; Fröhlich, Jenny; Atanassov, Ilian; Mann, Matthias; Beyer, Andreas; Partridge, Linda.
In: eLife, Vol. 10, 21.04.2021.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila
AU - Tain, Luke Stephen
AU - Sehlke, Robert
AU - Meilenbrock, Ralf Leslie
AU - Leech, Thomas
AU - Paulitz, Jonathan
AU - Chokkalingam, Manopriya
AU - Nagaraj, Nagarjuna
AU - Grönke, Sebastian
AU - Fröhlich, Jenny
AU - Atanassov, Ilian
AU - Mann, Matthias
AU - Beyer, Andreas
AU - Partridge, Linda
N1 - © 2021, Tain et al.
PY - 2021/4/21
Y1 - 2021/4/21
N2 - 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.
AB - 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.
U2 - 10.7554/eLife.67275
DO - 10.7554/eLife.67275
M3 - Journal article
C2 - 33879316
VL - 10
JO - eLife
JF - eLife
SN - 2050-084X
ER -
ID: 261519576