title: Aging in heterozygous Dnmt1-deficient mice: effects on survival, the DNA methylation genes, and the development of amyloidosis.
abstract: We previously reported that heterozygous DNA methyltransferase 1-deficient (Dnmt1(+/-)) mice maintain T-cell immune function and DNA methylation levels with aging, whereas controls develop autoimmunity, immune senescence, and DNA hypomethylation. We therefore compared survival, cause of death, and T-cell DNA methylation gene expression during aging in Dnmt1(+/-) mice and controls. No difference in longevity was observed, but greater numbers of Dnmt1(+/-) mice developed jejunal apolipoprotein AII amyloidosis. Both groups showed decreased Dnmt1 expression with aging. However, expression of the de novo methyltransferases Dnmt3a and Dnmt3b increased with aging in stimulated T cells from control mice. MeCP2, a methylcytosine binding protein that participates in maintenance DNA methylation, increased with age in Dnmt1(+/-) mice, suggesting a mechanism for the sustained DNA methylation levels. This model thus provides potential mechanisms for DNA methylation changes of aging, and suggests that changes in DNA methylation may contribute to some forms of amyloidosis that develop with aging.
authors.affiliation: Department of Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Ray
authors.forename: Ailing
authors.initials: A
authors.lastname: Wu
authors.forename: J Erby
authors.initials: JE
authors.lastname: Wilkinson
authors.forename: Hedwig S
authors.initials: HS
authors.lastname: Murphy
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
authors.forename: Barbara
authors.initials: B
authors.lastname: Kluve-Beckerman
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Liepnieks
authors.forename: Merrill
authors.initials: M
authors.lastname: Benson
authors.forename: Raymond
authors.initials: R
authors.lastname: Yung
authors.forename: Bruce
authors.initials: B
authors.lastname: Richardson
mesh_terms: D000375:Aging / Q000502:physiology*; D000686:Amyloidosis / Q000209:etiology*; D000818:Animals; D002423:Cause of Death; D019175:DNA Methylation; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D012097:Repressor Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: C485852:Dmap1 protein, mouse; D012097:Repressor Proteins