Aging in heterozygous Dnmt1-deficient mice

Effects on survival, the DNA methylation genes, and the development of amyloidosis

Donna Ray, Ailing Wu, J. Erby Wilkinson, Hedwig S. Murphy, Qianjin Lu, Barbara Kluve-Beckerman, Juris J. Liepnieks, Merrill Benson, Raymond Yung, Bruce Richardson

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 Dnmt+/- 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.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume61
Issue number2
StatePublished - Feb 2006

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Amyloidosis
DNA Methylation
Genes
Methyltransferases
T-Lymphocytes
Apolipoprotein A-II
DNA
Autoimmunity
Cause of Death
Carrier Proteins
Maintenance
Gene Expression

ASJC Scopus subject areas

  • Aging

Cite this

Aging in heterozygous Dnmt1-deficient mice : Effects on survival, the DNA methylation genes, and the development of amyloidosis. / Ray, Donna; Wu, Ailing; Wilkinson, J. Erby; Murphy, Hedwig S.; Lu, Qianjin; Kluve-Beckerman, Barbara; Liepnieks, Juris J.; Benson, Merrill; Yung, Raymond; Richardson, Bruce.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 61, No. 2, 02.2006, p. 115-124.

Research output: Contribution to journalArticle

Ray, D, Wu, A, Wilkinson, JE, Murphy, HS, Lu, Q, Kluve-Beckerman, B, Liepnieks, JJ, Benson, M, Yung, R & Richardson, B 2006, 'Aging in heterozygous Dnmt1-deficient mice: Effects on survival, the DNA methylation genes, and the development of amyloidosis', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 61, no. 2, pp. 115-124.
Ray, Donna ; Wu, Ailing ; Wilkinson, J. Erby ; Murphy, Hedwig S. ; Lu, Qianjin ; Kluve-Beckerman, Barbara ; Liepnieks, Juris J. ; Benson, Merrill ; Yung, Raymond ; Richardson, Bruce. / Aging in heterozygous Dnmt1-deficient mice : Effects on survival, the DNA methylation genes, and the development of amyloidosis. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2006 ; Vol. 61, No. 2. pp. 115-124.
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