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, Laura | |
dc.contributor.author | Moiseeva, Victoria | |
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 | |
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 | |
dc.contributor.author | de Haan, Gerald | |
dc.contributor.author | Bischof, Oliver | |
dc.contributor.author | Gil, Jesús | |
dc.date.accessioned | 2023-11-06T13:58:17Z | |
dc.date.available | 2023-11-06T13:58:17Z | |
dc.date.issued | 2022-09 | |
dc.identifier.citation | Nat Aging. 2022 Sep:2:851-866. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16647 | |
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. | es_ES |
dc.description.sponsorship | We are grateful to members of J. Gil’s laboratory for reagents, comments and other
contributions to this project. We thank members of the Genomics LMS facility (L. Game,
K. Rekopoulou and A. Ivan) and the Bioinformatics LMS facility (G. Dharmalingam, M.
Karimi and H. Pallikonda) for help with RNA-seq and data processing. 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. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Histones | es_ES |
dc.subject.mesh | Cellular Senescence | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Tubercidin | es_ES |
dc.subject.mesh | Epigenesis, Genetic | es_ES |
dc.title | 3-deazaadenosine (3DA) alleviates senescence to promote cellular fitness and cell therapy efficiency in mice. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 36438588 | es_ES |
dc.format.volume | 2 | es_ES |
dc.format.page | 851 | es_ES |
dc.identifier.doi | 10.1038/s43587-022-00279-9 | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | Fundación La Marató TV3 | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2662-8465 | es_ES |
dc.relation.publisherversion | 10.1038/s43587-022-00279-9 | es_ES |
dc.identifier.journal | Nature aging | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Laboratorio de Regeneración Tisular | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/ERC-2016-AdG-741966 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17-00040 | es_ES |