Age- and sex-dependent DNA hypomethylation controlled by growth hormone in mouse liver

Masaki Takasugi, Koji Hayakawa, Daisuke Arai, Kunio Shiota*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


In mammals, differences in liver function and aging have been observed between sexes; however, the epigenetic mechanisms underlying such differences remain largely unexplored. In this study, we investigated sex- and age-dependent DNA methylation status in the mouse liver. We analyzed 90 known sex-differentially expressed genes, and identified sex-dependent methylation in Zfp809, Hsd3b5, Treh, Cxcl11, Cyp17a1, and Nnmt genes. After 4 weeks of age, we noted the gradual establishment of sex-dependent hypomethylation in each of these genes in either males or females. The exposure of male mice to female-like growth hormone (GH) profile repressed male-predominant hypomethylation and promoted female-predominant hypomethylation. The occurrence of age-dependent hypomethylation, including at loci for which we also observed sex-dependent changes in DNA methylation, was accompanied by the downregulation of DNMT3A/B. In addition, we found that age-dependent hypomethylation was promoted through liver regeneration induced by partial hepatectomy, suggesting that DNMT activities were not enough to retain methylation levels. In conclusion, our results demonstrate that sex-dependent GH profiles influence the age-progressive hypomethylation under decreased DNMT3A/B levels in certain regions of the genome.

Original languageEnglish
Pages (from-to)331-337
Number of pages7
JournalMechanisms of Ageing and Development
Issue number7-8
Publication statusPublished - 2013 Jul
Externally publishedYes


  • Aging
  • DNA hypomethylation
  • Growth hormone
  • Liver
  • Sex-difference

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology


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