Caloric restriction delays age-related methylation drift

Shinji Maegawa, Yue Lu, Tomomitsu Tahara, Justin T. Lee, Jozef Madzo, Shoudan Liang, Jaroslav Jelinek, Ricki J. Colman, Jean Pierre J. Issa

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65 Citations (Scopus)

Abstract

In mammals, caloric restriction consistently results in extended lifespan. Epigenetic information encoded by DNA methylation is tightly regulated, but shows a striking drift associated with age that includes both gains and losses of DNA methylation at various sites. Here, we report that epigenetic drift is conserved across species and the rate of drift correlates with lifespan when comparing mice, rhesus monkeys, and humans. Twenty-two to 30-year-old rhesus monkeys exposed to 30% caloric restriction since 7-14 years of age showed attenuation of age-related methylation drift compared to ad libitum-fed controls such that their blood methylation age appeared 7 years younger than their chronologic age. Even more pronounced effects were seen in 2.7-3.2-year-old mice exposed to 40% caloric restriction starting at 0.3 years of age. The effects of caloric restriction on DNA methylation were detectable across different tissues and correlated with gene expression. We propose that epigenetic drift is a determinant of lifespan in mammals.

Original languageEnglish
Article number539
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 01-12-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Maegawa, S., Lu, Y., Tahara, T., Lee, J. T., Madzo, J., Liang, S., Jelinek, J., Colman, R. J., & Issa, J. P. J. (2017). Caloric restriction delays age-related methylation drift. Nature Communications, 8(1), [539]. https://doi.org/10.1038/s41467-017-00607-3