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3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice

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Title: 3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice
Authors: Guerrero, A
Innes, AJ
Roux, P-F
Buisman, SC
Jung, J
Ortet, L
Moiseeva, V
Wagner, V
Robinson, L
Ausema, A
Potapova, A
Perdiguero, E
Weersing, E
Aarts, M
Martin, N
Wuestefeld, T
Muñoz-Cánoves, P
De Haan, G
Bischof, O
Gil, J
Item Type: Journal Article
Abstract: 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 inhibitor, alleviates replicative and oncogene-induced senescence. 3DA-treated senescent cells showed reduced global histone H3 lysine 36 trimethylation, 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. Notably, 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 cells in immunocompromised mice. Together, our results identify 3DA as a promising drug enhancing the efficiency of cellular therapies by restraining senescence.
Issue Date: 1-Sep-2022
Date of Acceptance: 4-Aug-2022
URI: http://hdl.handle.net/10044/1/100501
DOI: 10.1038/s43587-022-00279-9
ISSN: 2662-8465
Publisher: Nature Research
Start Page: 851
End Page: 866
Journal / Book Title: Nature Aging
Volume: 2
Copyright Statement: © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
Publication Status: Published
Online Publication Date: 2022-09-13
Appears in Collections:Department of Immunology and Inflammation
Institute of Clinical Sciences