title: Distinct cellular and molecular environments support aging-related DNA methylation changes in the substantia nigra.
abstract: We aimed to couple brain region-specific changes in global DNA methylation over aging to underlying cellular and molecular environments.
  
  
  
  We measured two major forms of DNA methylation and analyzed Dnmt, Tet and metabolite levels in the striatum and substantia nigra (SN) over aging in healthy male mice.
  
  
  
  The ratio of 5-hydroxymethylcytosine to 5-methylcytosine increases over aging in the SN, and 5-hydroxymethylcytosine increases preferentially in dopaminergic neurons. Additionally, this age-dependent alteration in methylation correlates with a reduction in the ratio of α-ketoglutarate to succinate in the SN.
  
  
  
  Distinct cellular and molecular environments correlate with aging-associated methylation changes in the SN, implicating this epigenetic mechanism in the susceptibility of this brain region to age-related cell loss.
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Fasolino
authors.affiliation: Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521, USA.|Department of Chemistry, University of California, Riverside, CA 92521, USA.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhaolan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D007656:Ketoglutaric Acids / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013378:Substantia Nigra / Q000254:growth & development / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D007656:Ketoglutaric Acids; D044503:5-Methylcytosine; D019802:Succinic Acid; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: 5-hydroxymethylcytosine; 5-methylcytosine; DNA methylation; DNMTs; TETs; aging; dopaminergic; striatum; substantia nigra; α-ketoglutarate