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Объяснения фактора старения кодовой модуляцией возраста активирующими экзосомальными РНК



zoldrax:

Вышло две работы, показывающие возможность объяснения фактора старения кодовой модуляцией возраста активирующими экзосомальными РНК.

1. Стволовые клетки гипоталамуса частично контролируют скорость старения через экзосомальные микроРНК
Hypothalamic stem cells control ageing speed partly through exosomal miRNAs
http://rdcu.be/uJ6e

2. Сборник статей про активирующие РНК, который показывает принципиальную возможность кодовой (матричной) модуляции
RNA Activation
https://www.springer.com/gp/book/9789811043093





1.


Nature       https://www.nature.com/articles/nature23282      PDF


Hypothalamic stem cells control ageing speed partly through exosomal miRNAs




Received:03 July 2016Accepted:12 June 2017 Published online:26 July 2017


Abstract


It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.


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Acknowledgements


This study was supported by NIH R01 DK078750, AG031774, HL113180 and DK099136 (D.C.).


Affiliations


Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York 10461, USA




    • Yalin Zhang
    • Min Soo Kim
    • Baosen Jia
    • Jingqi Yan
    • Juan Pablo Zuniga-Hertz
    • Cheng Han
    • Dongsheng Cai



Contributions


Y.Z., M.S.K., J.Y. and C.H. performed hypothalamic injections and cell implantation; Y.Z. performed immunostaining, cloning, virus production and CSF sampling; M.S.K. performed behavioural experiments and exosome treatment; B.J. performed cell culture, exosome and miRNA characterization; J.Y. performed lifespan follow-up and initial behavioural and miRNA analysis; J.P.Z.-H. performed cell culture and imaging; D.C. conceived the hypothesis, designed and organized the study and wrote the paper.


Corresponding author


Correspondence to Dongsheng Cai.

Reviewer Information Nature thanks K. Jin, T. Wyss-Coray and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Extended data


Extended data figures



  1. 1.

    Ageing-related physiology and histology in C57BL/6 mice.

  2. 2.

    Viral injection and additional information on TK1/GCV model.

  3. 3.

    Ablation of htNSCs in hypothalamic third ventricular wall by DTR/diphtheria toxin.

  4. 4.

    Assessing exosomes secreted by htNSCs.

  5. 5.

    Additional assessments on secreted exosomes from htNSCs.

  6. 6.

    Small RNA bio-analyser assay of secreted exosomes.

  7. 7.

    Growth factors and cytokines secreted by htNSCs.

  8. 8.

    Effects on htNSCs and animal physiology by Rab27a shRNA.

  9. 9.

    Electron microscopic examination of htNSC-secreted exosomes.

  10. 10.

    Additional information for the anti-ageing models used in this study.



Supplementary information PDF files



  1. 1.

    Supplementary Figure 1

    This file contains uncropped images of all western blots shown in the manuscript.



Excel files



  1. 1.

    Supplementary Data 1

    This file contains microarray data of Figure 4d.

  2. 2.

    Supplementary Data 2

    This file contains qPCR data of Figure 4e.








2.


https://www.springer.com/gp/book/9789811043093


© 2017RNA Activation Editors: Li, Long-Cheng (Ed.)





  • Provides a comprehensive knowledge of RNA activation


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This book offers an essential guide to RNA activation (RNAa), an emerging and fascinating new field. RNAa is a small RNA-guided and Argonaute-dependent gene regulation phenomenon in which promoter-targeted short double-stranded RNAs (dsRNAs) induce target gene expression at the transcriptional level. It occurs primarily in the nucleus and can be mediated by artificially designed short duplex RNAs that target regulatory sequences (e.g., promoters, genes’ 3’ termini and enhancers) and naturally occurring small RNAs (e.g., miRNAs and C. elegans 22G-RNAs).

With contributions from internationally respected RNA experts, this book provides comprehensive coverage of different RNAa mechanisms and a timely update on recent advances in RNAa research, with a focus on developing RNAa-based therapeutics. Special chapters are also devoted to the topics of gene activation induced by antisense oligonucleotides and the CRISPR system. As the first book to cover RNAa, it will be of interest to a wide audience, from scientists in academia and the pharmaceutical industry to clinicians who wish to further explore the biology of RNAa and related phenomena, so as to harness their full potential for use in biotechnology and drug development.


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Table of contents (16 chapters)




  • Small RNA-Guided Transcriptional Gene Activation (RNAa) in Mammalian Cells

    Li, Long-Cheng

    Pages 1-20

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  • Enhancing Neuronogenesis and Counteracting Neuropathogenic Gene Haploinsufficiencies by RNA Gene Activation

    Mallamaci, Antonello

    Pages 23-39

  • Target-Recognition Mechanism and Specificity of RNA Activation

    Cao, Huiqing (et al.)

    Pages 41-51

  • Promoter-Targeted Small Activating RNAs Alter Nucleosome Positioning

    Wang, Bin (et al.)

    Pages 53-61

  • Endogenous miRNAa: miRNA-Mediated Gene Upregulation

    Huang, Vera

    Pages 65-79


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