Imperial College London
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DrAndrewInnes

Faculty of Medicine, Department of Immunology and Inflammation

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 4017a.innes

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Guerrero:2022:10.1038/s43587-022-00279-9,
author = {Guerrero, A and Innes, AJ and Roux, P-F and Buisman, SC and Jung, J and Ortet, L and Moiseeva, V and Wagner, V and Robinson, L and Ausema, A and Potapova, A and Perdiguero, E and Weersing, E and Aarts, M and Martin, N and Wuestefeld, T and Muñoz-Cánoves, P and de, Haan G and Bischof, O and Gil, J},
doi = {10.1038/s43587-022-00279-9},
journal = {Nature Aging},
pages = {851--866},
title = {3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice},
url = {http://dx.doi.org/10.1038/s43587-022-00279-9},
volume = {2},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Guerrero,A
AU  - Innes,AJ
AU  - Roux,P-F
AU  - Buisman,SC
AU  - Jung,J
AU  - Ortet,L
AU  - Moiseeva,V
AU  - Wagner,V
AU  - Robinson,L
AU  - Ausema,A
AU  - Potapova,A
AU  - Perdiguero,E
AU  - Weersing,E
AU  - Aarts,M
AU  - Martin,N
AU  - Wuestefeld,T
AU  - Muñoz-Cánoves,P
AU  - de,Haan G
AU  - Bischof,O
AU  - Gil,J
DO  - 10.1038/s43587-022-00279-9
EP  - 866
PY  - 2022///
SN  - 2662-8465
SP  - 851
TI  - 3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice
T2  - Nature Aging
UR  - http://dx.doi.org/10.1038/s43587-022-00279-9
UR  - http://hdl.handle.net/10044/1/100501
VL  - 2
ER  -
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