000 | 02547 am a22004213u 4500 | ||
---|---|---|---|
042 | _adc | ||
100 | 1 | 0 |
_aGuerrero, Ana _eauthor _91625 |
700 | 1 | 0 |
_aInnes, Andrew J. _eauthor _91626 |
700 | 1 | 0 |
_aRoux, Pierre-François _eauthor _91627 |
700 | 1 | 0 |
_aBuisman, Sonja C. _eauthor _91628 |
700 | 1 | 0 |
_aJung, Johannes _eauthor _91629 |
700 | 1 | 0 |
_aOrtet, Laura _eauthor _91630 |
700 | 1 | 0 |
_aMoiseeva, Victoria _eauthor _91631 |
700 | 1 | 0 |
_aWagner, Verena _eauthor _91632 |
700 | 1 | 0 |
_aRobinson, Lucas _eauthor _91633 |
700 | 1 | 0 |
_aAusema, Albertina _eauthor _91634 |
700 | 1 | 0 |
_aPotapova, Anna _eauthor _91635 |
700 | 1 | 0 |
_aPerdiguero, Eusebio _eauthor _91636 |
700 | 1 | 0 |
_aWeersing, Ellen _eauthor _91637 |
700 | 1 | 0 |
_aAarts, Marieke _eauthor _91638 |
700 | 1 | 0 |
_aMartin, Nadine _eauthor _91639 |
700 | 1 | 0 |
_aWuestefeld, Torsten _eauthor _91640 |
700 | 1 | 0 |
_aMuñoz-Cánoves, Pura _eauthor _91641 |
700 | 1 | 0 |
_ade Haan, Gerald _eauthor _91642 |
700 | 1 | 0 |
_aBischof, Oliver _eauthor _91643 |
700 | 1 | 0 |
_aGil, Jesús _eauthor _91644 |
245 | 0 | 0 | _a3-deazaadenosine (3DA) alleviates senescence to promote cellular fitness and cell therapy efficiency in mice |
260 | _c2022-09. | ||
500 | _a/pmc/articles/PMC7613850/ | ||
500 | _a/pubmed/36438588 | ||
520 | _aCellular 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. | ||
540 | _a | ||
546 | _aen | ||
690 | _aArticle | ||
655 | 7 |
_aText _2local |
|
786 | 0 | _nNat Aging | |
856 | 4 | 1 |
_uhttp://dx.doi.org/10.1038/s43587-022-00279-9 _zConnect to this object online. |
999 |
_c1730 _d1730 |