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

Guerrero, A; Innes, AJ; Roux, PF; Buisman, SC; Jung, J; Ortet, L; Moiseeva, V; ... Gil, J; + view all (2022) 3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice. Nature Aging , 2 (9) pp. 851-866. 10.1038/s43587-022-00279-9. Green open access

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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.

Type: Article
Title: 3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s43587-022-00279-9
Publisher version: http://dx.doi.org/10.1038/s43587-022-00279-9
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Ageing, High-throughput screening, Senescence
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/10158280
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