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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Tain, Luke S. (VerfasserIn) , Sehlke, Robert (VerfasserIn) , Jain, Chirag (VerfasserIn) , Chokkalingam, Manopriya (VerfasserIn) , Nagaraj, Nagarjuna (VerfasserIn) , Essers, Paul (VerfasserIn) , Rassner, Mark (VerfasserIn) , Grönke, Sebastian (VerfasserIn) , Froelich, Jenny (VerfasserIn) , Dieterich, Christoph (VerfasserIn) , Mann, Matthias (VerfasserIn) , Alic, Nazif (VerfasserIn) , Beyer, Andreas (VerfasserIn) , Partridge, Linda (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 September 2017
In: Molecular systems biology
Year: 2017, Jahrgang: 13, Heft: 9, Pages: 1-19
ISSN:1744-4292
DOI:10.15252/msb.20177663
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/msb.20177663
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/msb.20177663
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 21.04.2020
Beschreibung:Online Resource
ISSN:1744-4292
DOI:10.15252/msb.20177663