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

23 April 2021

Tissue-specific transcriptional and proteomic profiling of long-lived Drosophila dilp2-3,5 mutants 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.

partridge insulin fly publication

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.

https://elifesciences.org/articles/67275