2026-04-29T12:23:47Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/166472024-09-21T10:49:28Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Guerrero, Ana
author
Innes, Andrew J
author
Roux, Pierre-François
author
Buisman, Sonja C
author
Jung, Johannes
author
Ortet, Laura
author
Moiseeva, Victoria
author
Wagner, Verena
author
Robinson, Lucas
author
Ausema, Albertina
author
Potapova, Anna
author
Perdiguero, Eusebio
author
Weersing, Ellen
author
Aarts, Marieke
author
Martin, Nadine
author
Wuestefeld, Torsten
author
Muñoz-Cánoves, Pura
author
de Haan, Gerald
author
Bischof, Oliver
author
Gil, Jesús
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación La Marató TV3
funder
Fundación La Caixa
2023-11-06T13:58:17Z
2023-11-06T13:58:17Z
2022-09
Nat Aging. 2022 Sep:2:851-866.
10.1038/s43587-022-00279-9
2662-8465
Nature aging
36438588
http://hdl.handle.net/20.500.12105/16647
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.
eng
3-deazaadenosine (3DA) alleviates senescence to promote cellular fitness and cell therapy efficiency in mice.
journal article
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3_deazaadenosine_Nat Aging_2022.pdf
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3_deazaadenosine_Nat Aging_2022.pdf.txt