title: Natural ageing in the rat liver correlates with progressive stabilisation of DNA-nuclear matrix interactions and withdrawal of genes from the nuclear substructure.
abstract: In the interphase nucleus, the DNA of higher eukaryotes is organised in supercoiled loops anchored to a nuclear matrix (NM). Replication, transcription and splicing seem to occur at macromolecular complexes organised upon the NM. Thus, the topological relationship between genes located in the loops and the NM appears to be very important for nuclear physiology. Here, we report that natural ageing in the rat liver correlates with a progressive strengthening of the NM framework and the stabilisation of the DNA loop-NM interactions, as well as with a progressive increase in the relative distance of genes to the NM. Both phenomena correlate with the gradual loss of proliferating potential and progression towards terminal differentiation in the hepatocytes, suggesting that wholesale modifications in the topological relationships within the cell nucleus are markers of tissue ageing and senescence, at least in the mammalian liver. We discuss the possible functional implications of such structural modifications that may underlie both terminal hepatocyte differentiation and their eventual replicative senescence.
authors.affiliation: Laboratorio de Biología Molecular, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca, Edo.
authors.forename: Apolinar
authors.initials: A
authors.lastname: Maya-Mendoza
authors.forename: Rolando
authors.initials: R
authors.lastname: Hernández-Muñoz
authors.forename: Patricio
authors.initials: P
authors.lastname: Gariglio
authors.forename: Armando
authors.initials: A
authors.lastname: Aranda-Anzaldo
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D004278:DNA, Superhelical / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D008297:Male; D015530:Nuclear Matrix / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004278:DNA, Superhelical; D046911:Macromolecular Substances