title: Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells.
abstract: 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.
  
  
  
  Here, we analyzed the genome-wide profile of 5hmc in mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2-89 years.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Estela G
authors.initials: EG
authors.lastname: Toraño
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Bayón
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Del Real
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Marta I
authors.initials: MI
authors.lastname: Sierra
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: María G
authors.initials: MG
authors.lastname: García
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Antonella
authors.initials: A
authors.lastname: Carella
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Thalia
authors.initials: T
authors.lastname: Belmonte
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Rocío G
authors.initials: RG
authors.lastname: Urdinguio
authors.affiliation: Unidad de Biotecnología Celular, Área de Genética Humana, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cubillo
authors.affiliation: Unidad de Biotecnología Celular, Área de Genética Humana, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Castro
authors.affiliation: Department of Internal Medicine, Hospital U.M. Valdecilla, University of Cantabria, IDIVAL, Santander, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Delgado-Calle
authors.affiliation: Department of Internal Medicine, Hospital U.M. Valdecilla, University of Cantabria, IDIVAL, Santander, Spain.
authors.forename: Flor M
authors.initials: FM
authors.lastname: Pérez-Campo
authors.affiliation: Department of Internal Medicine, Hospital U.M. Valdecilla, University of Cantabria, IDIVAL, Santander, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
authors.affiliation: Nanomaterials and Nanotechnology Research Center (CINN-CSIC)-Universidad de Oviedo-Principado de Asturias, El Entrego, Spain. mffraga@cinn.es.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain. affernandez@hca.es.
authors.forename: Agustín F
authors.identifier: 0000-0002-3792-4085
authors.initials: AF
authors.lastname: Fernández
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001854:Bone Marrow Cells / Q000166:cytology*; D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D002843:Chromatin; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine
keywords: 5hmC; Aging; Bone-marrow; Epigenetics; MSCs