Ageing-associated small RNA cargo of extracellular vesicles

Previous work on murine models and humans demonstrated global as well as tissue-specific molecular ageing trajectories of RNAs. Extracellular vesicles (EVs) are membrane vesicles mediating the horizontal transfer of genetic information between different tissues. We sequenced small regulatory RNAs (s...

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Bibliographic Details
Published in:RNA biology 2023-12, Vol.20 (1), p.482-494
Main Authors: Kern, Fabian, Kuhn, Thomas, Ludwig, Nicole, Simon, Martin, Gröger, Laura, Fabis, Natalie, Aparicio-Puerta, Ernesto, Salhab, Abdulrahman, Fehlmann, Tobias, Hahn, Oliver, Engel, Annika, Wagner, Viktoria, Koch, Marcus, Winek, Katarzyna, Soreq, Hermona, Nazarenko, Irina, Fuhrmann, Gregor, Wyss-Coray, Tony, Meese, Eckart, Keller, Verena, Laschke, Matthias W., Keller, Andreas
Format: Article
Language:English
Subjects:
Aging - genetics
Animals
Biological Sciences
extracellular vesicles
Extracellular Vesicles - metabolism
genes
Humans
longevity
Mice
microRNA
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Noncoding RNA
plasma
Research Paper
RNA, Small Untranslated - genetics
RNA, Small Untranslated - metabolism
RNA, Transfer - metabolism
tissue ageing
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Summary:Previous work on murine models and humans demonstrated global as well as tissue-specific molecular ageing trajectories of RNAs. Extracellular vesicles (EVs) are membrane vesicles mediating the horizontal transfer of genetic information between different tissues. We sequenced small regulatory RNAs (sncRNAs) in two mouse plasma fractions at five time points across the lifespan from 2-18 months: (1) sncRNAs that are free-circulating (fc-RNA) and (2) sncRNAs bound outside or inside EVs (EV-RNA). Different sncRNA classes exhibit unique ageing patterns that vary between the fcRNA and EV-RNA fractions. While tRNAs showed the highest correlation with ageing in both fractions, rRNAs exhibited inverse correlation trajectories between the EV- and fc-fractions. For miRNAs, the EV-RNA fraction was exceptionally strongly associated with ageing, especially the miR-29 family in adipose tissues. Sequencing of sncRNAs and coding genes in fat tissue of an independent cohort of aged mice up to 27 months highlighted the pivotal role of miR-29a-3p and miR-29b-3p in ageing-related gene regulation that we validated in a third cohort by RT-qPCR.
ISSN:1547-6286
1555-8584
1555-8584
DOI:10.1080/15476286.2023.2234713