2024-03-29T10:43:44Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1731582020-12-10T15:59:10Zcom_10261_28457com_10261_3col_10261_28462
00925njm 22002777a 4500
dc
Toraño, Estela G.
author
Bayón, Gustavo F.
author
Real, Álvaro del
author
Sierra, Marta I.
author
García, María G.
author
Carella, Antonella
author
Belmonte, Thalia
author
Urdinguio, Rocío G.
author
Cubillo, Isabel
author
García-Castro, Javier
author
Delgado-Calle, Jesús
author
Pérez-Campo, Flor M.
author
Riancho, José A.
author
Fraga, Mario F.
author
Fernández, Agustín F.
author
2016
[Background]: Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5-hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role in the process. [Methods]: Here, we analyzed the genome-wide profile of 5hmc in mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2-89 years. [Results]: We identified 10,685 frequently hydroxymethylated CpG sites in MSCs that were, as in other cell types, significantly associated with low density CpG regions, introns, the histone posttranslational modification H3k4me1 and enhancers. Study of the age-associated changes to 5hmC identified 785 hyper- and 846 hypo-hydroxymethylated CpG sites in the MSCs obtained from older individuals. [Conclusions]: DNA hyper-hydroxymethylation in the advanced-age group was associated with loss of 5mC, which suggests that, at specific CpG sites, this epigenetic modification might play a role in DNA methylation changes during lifetime. Since bone-marrow MSCs have many clinical applications, and the fact that the epigenomic alterations in this cell type associated with aging identified in this study could have associated functional effects, the age of donors should be taken into account in clinical settings.
Journal of Translational Medicine 14: 207 (2016)
http://hdl.handle.net/10261/173158
10.1186/s12967-016-0966-x
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/100008054
http://dx.doi.org/10.13039/501100002704
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.13039/100011941
27393146
Bone marrow
Epigenetics
Aging
MSCs
5hmC
Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells