Vesicle-bound regulatory RNAs are associated with tissue aging

Vesicle-bound regulatory RNAs are associated with tissue aging. Kern, F., Kuhn, T., Ludwig, N., Simon, M., Gröger, L., Fabis, N., Salhab, A., Fehlmann, T., Hahn, O., Engel, A., Koch, M., Koehler, J., Winek, K., Soreq, H., Fuhrmann, G., Wyss-Coray, T., Meese, E., Laschke, M. W., & Keller, A. bioRxiv, Cold Spring Harbor Laboratory, 2021.

Paper doi abstract bibtex

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 StatementThe authors have declared no competing interest.

@article {Kern2021.05.07.443093,
	author = {Kern, Fabian and Kuhn, Thomas and Ludwig, Nicole and Simon, Martin and Gr{\"o}ger, Laura and Fabis, Natalie and Salhab, Abdulrahman and Fehlmann, Tobias and Hahn, Oliver and Engel, Annika and Koch, Marcus and Koehler, Jana and Winek, Katarzyna and Soreq, Hermona and Fuhrmann, Gregor and Wyss-Coray, Tony and Meese, Eckart and Laschke, Matthias W. and Keller, Andreas},
	title = {Vesicle-bound regulatory RNAs are associated with tissue aging},
	elocation-id = {2021.05.07.443093},
	year = {2021},
	doi = {10.1101/2021.05.07.443093},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Previous work on murine models and human demonstrated global as well as tissue-specific molecular aging trajectories in solid tissues and body fluids1{\textendash}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 StatementThe authors have declared no competing interest.},
	URL = {https://www.biorxiv.org/content/early/2021/05/08/2021.05.07.443093},
	eprint = {https://www.biorxiv.org/content/early/2021/05/08/2021.05.07.443093.full.pdf},
	journal = {bioRxiv}
}

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