Abstract
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 language | English |
|---|---|
| Pages (from-to) | 331-337 |
| Number of pages | 7 |
| Journal | Mechanisms of Ageing and Development |
| Volume | 134 |
| Issue number | 7-8 |
| DOIs | |
| Publication status | Published - 2013 Jul |
| Externally published | Yes |
Keywords
- Aging
- DNA hypomethylation
- Growth hormone
- Liver
- Sex-difference
ASJC Scopus subject areas
- Ageing
- Developmental Biology