title: Increased age is associated with epigenetic and structural changes in chromatin from neuronal nuclei.
abstract: Chromatin organization has been considered to play a major role on aging, by regulating DNA accessibility to transcription and repair machinery. Such organization can be modulated by epigenetic events, such as DNA methylation and histone post-translational modifications. Since changes on gene expression profiles have been described in aged neurons, our aim was to study the age-dependent relationship between structural and epigenetic alterations on chromatin of cortical neurons from mice. For this purpose, isolated neuronal nuclei from mice of two ages were studied by image analysis after cytochemistry, or assessed for chromatin accessibility by enzymatic digestion. Additionally, two epigenetic marks, for open and for densely packed chromatin fibers were quantified. Results indicate epigenetically driven alterations on chromatin organization of cortical neurons with advancing age, whose fibers seem to undergo redistribution and unpackaging. Since increased transcriptional activity is not characteristic of aged neurons, these loosened chromatin fibers may be associated with impaired genome stability, as well as with increased accessibility of repair machinery to a life span damaged DNA.
authors.affiliation: Cytology, Histology, and Embryology Section, Institute of Biomedical Sciences, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, 38400-902, Brazil.
authors.forename: Henrique F
authors.initials: HF
authors.lastname: Rodrigues
authors.forename: Tafarel A
authors.initials: TA
authors.lastname: Souza
authors.forename: Flavia G
authors.initials: FG
authors.lastname: Ghiraldini
authors.forename: Maria Luiza S
authors.initials: ML
authors.lastname: Mello
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Moraes
mesh_terms: D000107:Acetylation; D000375:Aging / Q000235:genetics*; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure*; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000502:physiology*
chemical_list: D002843:Chromatin; D006657:Histones
keywords: AGING; CHROMATIN; EPIGENETICS; NEURONS