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Vesicle-bound regulatory RNAs are associated with tissue aging

View ORCID ProfileFabian Kern, View ORCID ProfileThomas Kuhn, View ORCID ProfileNicole Ludwig, View ORCID ProfileMartin Simon, View ORCID ProfileLaura Gröger, Natalie Fabis, View ORCID ProfileAbdulrahman Salhab, View ORCID ProfileTobias Fehlmann, View ORCID ProfileOliver Hahn, View ORCID ProfileAnnika Engel, Marcus Koch, Jana Koehler, View ORCID ProfileKatarzyna Winek, View ORCID ProfileHermona Soreq, View ORCID ProfileGregor Fuhrmann, View ORCID ProfileTony Wyss-Coray, View ORCID ProfileEckart Meese, View ORCID ProfileMatthias W. Laschke, View ORCID ProfileAndreas Keller
doi: https://doi.org/10.1101/2021.05.07.443093
Fabian Kern
1Chair for Clinical Bioinformatics, Saarland Informatics Campus, Saarland University, 66123 Saarbrücken, Germany
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  • ORCID record for Fabian Kern
Thomas Kuhn
2Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), Biogenic Nanotherapeutics group (BION), 66123 Saarbrücken, Germany
3Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany
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Nicole Ludwig
4Department of Human Genetics, Saarland University, 66421 Homburg, Germany
5Center for Human and Molecular Biology, Saarland University, 66421 Homburg, Germany
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Martin Simon
6Department of Biochemistry, Wuppertal University, 42119 Wuppertal, Germany
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Laura Gröger
4Department of Human Genetics, Saarland University, 66421 Homburg, Germany
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Natalie Fabis
6Department of Biochemistry, Wuppertal University, 42119 Wuppertal, Germany
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Abdulrahman Salhab
7Department of Genetics and Epigenetics, Saarland University, 66123 Saarbrücken, Germany
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  • ORCID record for Abdulrahman Salhab
Tobias Fehlmann
1Chair for Clinical Bioinformatics, Saarland Informatics Campus, Saarland University, 66123 Saarbrücken, Germany
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Oliver Hahn
8Department of Neurology and Neurological Sciences, Stanford University, Stanford, 94304 CA, USA
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Annika Engel
9German Research Center for Artificial Intelligence, 66123 Saarbrücken, Germany
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Marcus Koch
10INM – Leibniz Institute for New Materials, Campus D2 2, 66123 Saarbrücken, Germany
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Jana Koehler
9German Research Center for Artificial Intelligence, 66123 Saarbrücken, Germany
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Katarzyna Winek
11The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
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Hermona Soreq
11The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
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Gregor Fuhrmann
2Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), Biogenic Nanotherapeutics group (BION), 66123 Saarbrücken, Germany
3Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany
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Tony Wyss-Coray
8Department of Neurology and Neurological Sciences, Stanford University, Stanford, 94304 CA, USA
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Eckart Meese
4Department of Human Genetics, Saarland University, 66421 Homburg, Germany
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Matthias W. Laschke
12Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany
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Andreas Keller
1Chair for Clinical Bioinformatics, Saarland Informatics Campus, Saarland University, 66123 Saarbrücken, Germany
8Department of Neurology and Neurological Sciences, Stanford University, Stanford, 94304 CA, USA
13Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany
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  • ORCID record for Andreas Keller
  • For correspondence: andreas.keller@ccb.uni-saarland.de
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Abstract

Previous work on murine models and human demonstrated global as well as tissue-specific molecular aging trajectories in solid tissues and body fluids1–8. Extracellular vesicles like exosomes play a crucial role in communication and information exchange in between such systemic factors and solid tissues9,10. We sequenced freely circulating and vesicle-bound small regulatory RNAs in mice at five time points across the average life span from 2 to 18 months. Intriguingly, each small RNA class exhibits unique aging patterns, which showed differential signatures between vesicle-bound and freely circulating molecules. In particular, tRNA fragments showed overall highest correlation with aging which also matched well between sample types, facilitating age prediction with non-negative matrix factorization (86% accuracy). Interestingly, rRNAs exhibited inverse correlation trajectories between vesicles and plasma while vesicle-bound microRNAs (miRNAs) were exceptionally strong associated with aging. Affected miRNAs regulate the inflammatory response and transcriptional processes, and adipose tissues show considerable effects in associated gene regulatory modules. Finally, nanoparticle tracking and electron microscopy suggest a shift from overall many small to fewer but larger vesicles in aged plasma, potentially contributing to systemic aging trajectories and affecting the molecular aging of organs.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted May 08, 2021.
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Vesicle-bound regulatory RNAs are associated with tissue aging
Fabian Kern, Thomas Kuhn, Nicole Ludwig, Martin Simon, Laura Gröger, Natalie Fabis, Abdulrahman Salhab, Tobias Fehlmann, Oliver Hahn, Annika Engel, Marcus Koch, Jana Koehler, Katarzyna Winek, Hermona Soreq, Gregor Fuhrmann, Tony Wyss-Coray, Eckart Meese, Matthias W. Laschke, Andreas Keller
bioRxiv 2021.05.07.443093; doi: https://doi.org/10.1101/2021.05.07.443093
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Vesicle-bound regulatory RNAs are associated with tissue aging
Fabian Kern, Thomas Kuhn, Nicole Ludwig, Martin Simon, Laura Gröger, Natalie Fabis, Abdulrahman Salhab, Tobias Fehlmann, Oliver Hahn, Annika Engel, Marcus Koch, Jana Koehler, Katarzyna Winek, Hermona Soreq, Gregor Fuhrmann, Tony Wyss-Coray, Eckart Meese, Matthias W. Laschke, Andreas Keller
bioRxiv 2021.05.07.443093; doi: https://doi.org/10.1101/2021.05.07.443093

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