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Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice.

Publication ,  Journal Article
Mattocks, DAL; Mentch, SJ; Shneyder, J; Ables, GP; Sun, D; Richie, JP; Locasale, JW; Nichenametla, SN
Published in: Exp Gerontol
February 2017

Despite well-documented evidence for lifespan extension by methionine restriction (MR), underlying mechanisms remain unknown. As methionine can alter S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the substrate and product of DNA methyltransferase-1 (DNMT1), we hypothesized that MR diet alters DNA methylation. Young (8-week-old) and adult (1-year-old) male C57BL/6J mice were fed diets with different levels of methionine (0.12%-MR, 0.84%-CD) for 12weeks. Functional indicators of DNA methylation, including global methylation (GM), gene-specific methylation (GSM) and LINE-1 methylation; and biochemical factors affecting DNA methylation, SAH, SAM, and DNMT1 were assessed in different tissues. MR altered DNA methylation depending on the age of intervention. While MR had no effect on hepatic GM in young animals, it increased GM by 27% over CD in adults (p<0.01). In comparison with young animals, hepatic GM levels were 17% lower in CD adults (p<0.05), but not different in MR adults. The MR-induced increase in hepatic GM was associated with a 38% decrease in SAH levels in adults (p<0.001), with SAH and GM levels being negatively correlated (r2=0.33, p<0.001). No changes were observed in DNMT protein levels in liver. In adipose tissue, MR caused a 6% decline in GM in adults (p<0.05), a corresponding 2-fold increase in SAH (p<0.05), and a 2-fold decrease in DNMT1 (p<0.01). MR caused both increases and decreases in GSM of liver and adipose. No changes were observed in LINE-1. Together, these findings provide evidence for protective effects of MR diet on hepatic DNA hypomethylation in adults, apparently mediated by SAH. These findings also indicate that altered DNA methylation might be playing a role in benefits conferred by MR diet.

Duke Scholars

Published In

Exp Gerontol

DOI

EISSN

1873-6815

Publication Date

February 2017

Volume

88

Start / End Page

1 / 8

Location

England

Related Subject Headings

  • Time Factors
  • Mice, Inbred C57BL
  • Mice
  • Methionine
  • Male
  • Liver
  • Gerontology
  • Diet
  • DNA Methylation
  • Caloric Restriction
 

Citation

APA
Chicago
ICMJE
MLA
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Mattocks, D. A. L., Mentch, S. J., Shneyder, J., Ables, G. P., Sun, D., Richie, J. P., … Nichenametla, S. N. (2017). Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice. Exp Gerontol, 88, 1–8. https://doi.org/10.1016/j.exger.2016.12.003
Mattocks, Dwight A. L., Samantha J. Mentch, Jelena Shneyder, Gene P. Ables, Dongxiao Sun, John P. Richie, Jason W. Locasale, and Sailendra N. Nichenametla. “Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice.Exp Gerontol 88 (February 2017): 1–8. https://doi.org/10.1016/j.exger.2016.12.003.
Mattocks DAL, Mentch SJ, Shneyder J, Ables GP, Sun D, Richie JP, et al. Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice. Exp Gerontol. 2017 Feb;88:1–8.
Mattocks, Dwight A. L., et al. “Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice.Exp Gerontol, vol. 88, Feb. 2017, pp. 1–8. Pubmed, doi:10.1016/j.exger.2016.12.003.
Mattocks DAL, Mentch SJ, Shneyder J, Ables GP, Sun D, Richie JP, Locasale JW, Nichenametla SN. Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice. Exp Gerontol. 2017 Feb;88:1–8.
Journal cover image

Published In

Exp Gerontol

DOI

EISSN

1873-6815

Publication Date

February 2017

Volume

88

Start / End Page

1 / 8

Location

England

Related Subject Headings

  • Time Factors
  • Mice, Inbred C57BL
  • Mice
  • Methionine
  • Male
  • Liver
  • Gerontology
  • Diet
  • DNA Methylation
  • Caloric Restriction