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A proteomic atlas of insulin signalling reveals tissue-specific mechanisms of longevity assurance

Abstract 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 lifespa...

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Main Authors: Tain, Luke S. (Author) , Sehlke, Robert (Author) , Jain, Chirag (Author) , Chokkalingam, Manopriya (Author) , Nagaraj, Nagarjuna (Author) , Essers, Paul (Author) , Rassner, Mark (Author) , Grönke, Sebastian (Author) , Froelich, Jenny (Author) , Dieterich, Christoph (Author) , Mann, Matthias (Author) , Alic, Nazif (Author) , Beyer, Andreas (Author) , Partridge, Linda (Author)
Format: Article (Journal)
Language:English
Published: 15 September 2017
In: Molecular systems biology
Year: 2017, Volume: 13, Issue: 9, Pages: 1-19
ISSN:1744-4292
DOI:10.15252/msb.20177663
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/msb.20177663
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/msb.20177663
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Author Notes:Luke S Tain, Robert Sehlke, Chirag Jain, Manopriya Chokkalingam, Nagarjuna Nagaraj, Paul Essers, Mark Rassner, Sebastian Grönke, Jenny Froelich, Christoph Dieterich, Matthias Mann, Nazif Alic, Andreas Beyer, Linda Partridge
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Summary:Abstract 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.
Item Description:Gesehen am 21.04.2020
Physical Description:Online Resource
ISSN:1744-4292
DOI:10.15252/msb.20177663

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