2026-04-29T12:23:39Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/166472024-09-21T10:49:28Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2022-09 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. 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 3-deazaadenosine (3DA) alleviates senescence to promote cellular fitness and cell therapy efficiency in mice.