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3-deazaadenosine (3DA) alleviates senescence to promote cellular fitness and cell therapy efficiency in mice (Record no. 1730)

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Personal name Guerrero, Ana
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9 (RLIN) 1625
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Title 3-deazaadenosine (3DA) alleviates senescence to promote cellular fitness and cell therapy efficiency in mice
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Date of publication, distribution, etc. 2022-09.
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General note /pmc/articles/PMC7613850/
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General note /pubmed/36438588
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Summary, etc. Cellular senescence is a stable type of cell cycle arrest triggered by different stresses. As such, senescence drives age-related diseases and curbs cellular replicative potential. Here, we show that 3-deazaadenosine (3DA), an S-adenosyl homocysteinase (AHCY) inhibitor, alleviates replicative and oncogene-induced senescence. 3DA-treated senescent cells showed reduced global Histone H3 Lysine 36 trimethylation (H3K36me3), an epigenetic modification that marks the bodies of actively transcribed genes. By integrating transcriptome and epigenome data, we demonstrate that 3DA treatment affects key factors of the senescence transcriptional program. Remarkably, 3DA treatment alleviated senescence and increased the proliferative and regenerative potential of muscle stem cells from very old mice in vitro and in vivo. Moreover, ex vivo 3DA treatment was sufficient to enhance the engraftment of human umbilical cord blood (UCB) cells in immunocompromised mice. Together, our results identify 3DA as a promising drug enhancing the efficiency of cellular therapies by restraining senescence.
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Language note en
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Personal name Innes, Andrew J.
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9 (RLIN) 1626
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Personal name Roux, Pierre-François
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9 (RLIN) 1627
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Personal name Buisman, Sonja C.
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9 (RLIN) 1628
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Personal name Jung, Johannes
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9 (RLIN) 1629
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Personal name Ortet, Laura
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9 (RLIN) 1630
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Personal name Moiseeva, Victoria
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9 (RLIN) 1631
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Personal name Wagner, Verena
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9 (RLIN) 1632
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Personal name Robinson, Lucas
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9 (RLIN) 1633
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Personal name Ausema, Albertina
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9 (RLIN) 1634
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Personal name Potapova, Anna
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9 (RLIN) 1635
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Personal name Perdiguero, Eusebio
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9 (RLIN) 1636
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Personal name Weersing, Ellen
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9 (RLIN) 1637
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Personal name Aarts, Marieke
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9 (RLIN) 1638
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Personal name Martin, Nadine
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9 (RLIN) 1639
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Personal name Wuestefeld, Torsten
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9 (RLIN) 1640
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Personal name Muñoz-Cánoves, Pura
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9 (RLIN) 1641
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Personal name de Haan, Gerald
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9 (RLIN) 1642
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Personal name Bischof, Oliver
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9 (RLIN) 1643
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Personal name Gil, Jesús
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9 (RLIN) 1644
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Note Nat Aging
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1038/s43587-022-00279-9">http://dx.doi.org/10.1038/s43587-022-00279-9</a>
Public note Connect to this object online.

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