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 and Jean-Pierre J. Issa
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Shinji Maegawa: Lewis Katz School of Medicine at Temple University
Yue Lu: The University of Texas MD Anderson Cancer Center
Tomomitsu Tahara: Lewis Katz School of Medicine at Temple University
Justin T. Lee: Lewis Katz School of Medicine at Temple University
Jozef Madzo: Lewis Katz School of Medicine at Temple University
Shoudan Liang: The University of Texas MD Anderson Cancer Center
Jaroslav Jelinek: Lewis Katz School of Medicine at Temple University
Ricki J. Colman: University of Wisconsin
Jean-Pierre J. Issa: Lewis Katz School of Medicine at Temple University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00607-3

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