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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| Format: | Article |
| Language: | English |
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Springer Nature
2017-09-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20177663 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Luke S Tain |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b2ab6e59cb074d5c909331ce01d05a47 |
| institution | DOAJ |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-b2ab6e59cb074d5c909331ce01d05a472025-08-20T03:06:10ZengSpringer NatureMolecular Systems Biology1744-42922017-09-0113911910.15252/msb.20177663A proteomic atlas of insulin signalling reveals tissue‐specific mechanisms of longevity assuranceLuke S Tain0Robert Sehlke1Chirag Jain2Manopriya Chokkalingam3Nagarjuna Nagaraj4Paul Essers5Mark Rassner6Sebastian Grönke7Jenny Froelich8Christoph Dieterich9Matthias Mann10Nazif Alic11Andreas Beyer12Linda Partridge13Max‐Planck Institute for Biology of AgeingMax‐Planck Institute for Biology of AgeingMax‐Planck Institute for Biology of AgeingCECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated DiseasesDepartment of Proteomics and Signal Transduction, Max‐Planck‐Institute of BiochemistryMax‐Planck Institute for Biology of AgeingMax‐Planck Institute for Biology of AgeingMax‐Planck Institute for Biology of AgeingMax‐Planck Institute for Biology of AgeingSection of Bioinformatics and Systems Cardiology, Department of Internal Medicine III and Klaus Tschira Institute for Integrative Computational Cardiology, University of HeidelbergDepartment of Proteomics and Signal Transduction, Max‐Planck‐Institute of BiochemistryInstitute of Healthy Ageing, and GEE, UCLCECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated DiseasesMax‐Planck Institute for Biology of AgeingAbstract 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.https://doi.org/10.15252/msb.20177663ageinginsulin/IGFmitochondriaproteasomeproteome |
| spellingShingle | 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 A proteomic atlas of insulin signalling reveals tissue‐specific mechanisms of longevity assurance Molecular Systems Biology ageing insulin/IGF mitochondria proteasome proteome |
| title | A proteomic atlas of insulin signalling reveals tissue‐specific mechanisms of longevity assurance |
| title_full | A proteomic atlas of insulin signalling reveals tissue‐specific mechanisms of longevity assurance |
| title_fullStr | A proteomic atlas of insulin signalling reveals tissue‐specific mechanisms of longevity assurance |
| title_full_unstemmed | A proteomic atlas of insulin signalling reveals tissue‐specific mechanisms of longevity assurance |
| title_short | A proteomic atlas of insulin signalling reveals tissue‐specific mechanisms of longevity assurance |
| title_sort | proteomic atlas of insulin signalling reveals tissue specific mechanisms of longevity assurance |
| topic | ageing insulin/IGF mitochondria proteasome proteome |
| url | https://doi.org/10.15252/msb.20177663 |
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