Tain, Luke S., Sehlke, Robert, Jain, Chirag, Chokkalingam, Manopriya, Nagaraj, Nagarjuna, Essers, Paul, Rassner, Mark, Groenke, Sebastian, Froelich, Jenny, Dieterich, Christoph, Mann, Matthias, Alic, Nazif ORCID: 0000-0003-0356-6600, Beyer, Andreas ORCID: 0000-0002-3891-2123 and Partridge, Linda ORCID: 0000-0001-9615-0094 (2017). A proteomic atlas of insulin signalling reveals tissue-specific mechanisms of longevity assurance. Mol. Syst. Biol., 13 (9). HOBOKEN: WILEY. ISSN 1744-4292

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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 Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tain, Luke S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sehlke, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jain, ChiragUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chokkalingam, ManopriyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagaraj, NagarjunaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Essers, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rassner, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Groenke, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froelich, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dieterich, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mann, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alic, NazifUNSPECIFIEDorcid.org/0000-0003-0356-6600UNSPECIFIED
Beyer, AndreasUNSPECIFIEDorcid.org/0000-0002-3891-2123UNSPECIFIED
Partridge, LindaUNSPECIFIEDorcid.org/0000-0001-9615-0094UNSPECIFIED
URN: urn:nbn:de:hbz:38-219358
DOI: 10.15252/msb.20177663
Journal or Publication Title: Mol. Syst. Biol.
Volume: 13
Number: 9
Date: 2017
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1744-4292
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EXTENDS LIFE-SPAN; DROSOPHILA PGC-1 HOMOLOG; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; MITOCHONDRIAL ACTIVITY; TRANSCRIPTION FACTOR; DIETARY RESTRICTION; METABOLIC PATHWAYS; MASS-SPECTROMETRYMultiple languages
Biochemistry & Molecular BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21935

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