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

Autor: Tain LS; Max-Planck Institute for Biology of Ageing, Cologne, Germany., Sehlke R; Max-Planck Institute for Biology of Ageing, Cologne, Germany.; CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Jain C; Max-Planck Institute for Biology of Ageing, Cologne, Germany., Chokkalingam M; CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Nagaraj N; Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany., Essers P; Max-Planck Institute for Biology of Ageing, Cologne, Germany., Rassner M; Max-Planck Institute for Biology of Ageing, Cologne, Germany., Grönke S; Max-Planck Institute for Biology of Ageing, Cologne, Germany., Froelich J; Max-Planck Institute for Biology of Ageing, Cologne, Germany., Dieterich C; Section of Bioinformatics and Systems Cardiology, Department of Internal Medicine III and Klaus Tschira Institute for Integrative Computational Cardiology, University of Heidelberg, Heidelberg, Germany.; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg, Germany., Mann M; Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany., Alic N; Institute of Healthy Ageing, and GEE, UCL, London, UK., Beyer A; CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany andreas.beyer@uni-koeln.de partridge@age.mpg.de.; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Partridge L; Max-Planck Institute for Biology of Ageing, Cologne, Germany andreas.beyer@uni-koeln.de partridge@age.mpg.de.; Institute of Healthy Ageing, and GEE, UCL, London, UK.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2017 Sep 15; Vol. 13 (9), pp. 939. Date of Electronic Publication: 2017 Sep 15.
DOI: 10.15252/msb.20177663
Abstrakt: 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.
(© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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