dc.contributor.author |
Guerrero, Ana |
dc.contributor.author |
Innes, Andrew J. |
dc.contributor.author |
Roux, Pierre-François |
dc.contributor.author |
Buisman, Sonja C. |
dc.contributor.author |
Jung, Johannes |
dc.contributor.author |
Ortet Cortada, Laura |
dc.contributor.author |
Moiseeva, Victoria, 1992- |
dc.contributor.author |
Wagner, Verena |
dc.contributor.author |
Robinson, Lucas |
dc.contributor.author |
Ausema, Albertina |
dc.contributor.author |
Potapova, Anna |
dc.contributor.author |
Perdiguero, Eusebio, 1968- |
dc.contributor.author |
Weersing, Ellen |
dc.contributor.author |
Aarts, Marieke |
dc.contributor.author |
Martin, Nadine |
dc.contributor.author |
Wuestefeld, Torsten |
dc.contributor.author |
Muñoz Cánoves, Pura, 1962- |
dc.contributor.author |
Haan, Gerald de |
dc.contributor.author |
Bischof, Oliver |
dc.contributor.author |
Gil, Jesús |
dc.date.accessioned |
2023-04-28T06:05:45Z |
dc.date.available |
2023-04-28T06:05:45Z |
dc.date.issued |
2022 |
dc.identifier.citation |
Guerrero A, Innes AJ, Roux PF, 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. 3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice. Nat Aging. 2022;2(9):851–66. DOI: 10.1038/s43587-022-00279-9 |
dc.identifier.issn |
2662-8465 |
dc.identifier.uri |
http://hdl.handle.net/10230/56607 |
dc.description.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 (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. |
dc.description.sponsorship |
We thank O.C. Bing (BRC, A*STAR) for the histopathology scoring of liver sections. For the purpose of open access, the author has applied a Creative Commons Attribution license. Core support from MRC (MC_U120085810), a Development Gap Fund grant from LifeArc and Cancer Research UK (C15075/A28647) funded this research in J. Gil’s laboratory. P.M.-C. acknowledges funding from RTI2018-096068-B-I00, ERC-2016-AdG-741966, La Caixa HR17-00040, UPGRADE-H2020-825825, MWRF, Fundació La Marató-TV3, AFM, MDA and DPP-E. This work was supported by grants from the Deutsche Krebshilfe (to J.J.), the Dutch Cancer Society (to G.d.H.) and the Tekke Huizinga Fund (S.B. and G.d.H.). L.R. was supported by the Pasteur - Paris University International PhD Program and by the Fondation pour la Recherche Médicale. O.B was supported by Fondation ARC pour la Recherche sur le Cancer, INSERM-AGEMED and ANR S-ENCODE - 19-CE13-0017-01. O.B. is a Centre National de la Recherche Scientifique Research Director DR2. T.W. was funded by National Medical Research Council, Singapore through NMRC/OFLCG/003b/2018 and A*STAR through the Central Research Fund for Applied/Translational Research. |
dc.format.mimetype |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
Nature Research |
dc.relation.ispartof |
Nat Aging. 2022;2(9):851–66 |
dc.rights |
© Springer Nature Publishing AG Guerrero A, Innes AJ, Roux PF, Buisman SC, Jung J, Ortet L et al. 3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice. Nat Aging. 2022;2(9):851–66. DOI: 10.1038/s43587-022-00279-9 |
dc.title |
3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice |
dc.type |
info:eu-repo/semantics/article |
dc.identifier.doi |
http://dx.doi.org/10.1038/s43587-022-00279-9 |
dc.subject.keyword |
3DA |
dc.subject.keyword |
AHCY |
dc.subject.keyword |
Cord blood cells |
dc.subject.keyword |
Muscle stem cells |
dc.subject.keyword |
Senescence |
dc.relation.projectID |
info:eu-repo/grantAgreement/EC/H2020/741966 |
dc.relation.projectID |
info:eu-repo/grantAgreement/ES/2PE/RTI2018-096068-B-I00 |
dc.relation.projectID |
info:eu-repo/grantAgreement/EC/H2020/825825 |
dc.rights.accessRights |
info:eu-repo/semantics/openAccess |
dc.type.version |
info:eu-repo/semantics/acceptedVersion |