Tain, L.S., Sehlke, R., Jain, C., Chokkalingam, M., Nagaraj, N., Essers, P., Rassner, M., Grönke, S., Froelich, J., Dieterich, C., Mann, M., Alic, N., Beyer, A., Partridge, L. (2017). A proteomic atlas of insulin signalling reveals tissue-specific mechanisms of longevity assurance.  Mol. Syst. Biol. 13(9): 939.

FBrf0236658

Research paper

Lowered activity of the insulin/IGF signalling (IIS) network can ameliorate the effects of ageing in laboratory animals and, possibly, humans. Although transcriptome remodelling in long-lived IIS mutants has been extensively documented, the causal mechanisms contributing to extended lifespan, particularly in specific tissues, remain unclear. We have characterized the proteomes of four key insulin-sensitive tissues in a long-lived Drosophila IIS mutant and control, and detected 44% of the predicted proteome (6,085 proteins). Expression of ribosome-associated proteins in the fat body was reduced in the mutant, with a corresponding, tissue-specific reduction in translation. Expression of mitochondrial electron transport chain proteins in fat body was increased, leading to increased respiration, which was necessary for IIS-mediated lifespan extension, and alone sufficient to mediate it. Proteasomal subunits showed altered expression in IIS mutant gut, and gut-specific over-expression of the RPN6 proteasomal subunit, was sufficient to increase proteasomal activity and extend lifespan, whilst inhibition of proteasome activity abolished IIS-mediated longevity. Our study thus uncovered strikingly tissue-specific responses of cellular processes to lowered IIS acting in concert to ameliorate ageing.

PMC5615923 (PMC) (EuropePMC)