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Nat Commun. 2017 Sep 14;8(1):539. doi: 10.1038/s41467-017-00607-3.

Caloric restriction delays age-related methylation drift.

Author information

1
Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, 19140, USA. smaegawa@mdanderson.org.
2
Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. smaegawa@mdanderson.org.
3
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
4
Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, 19140, USA.
5
Department of Biostatistics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
6
Wisconsin National Primate Research Center and Department of Cell and Regenerative Biology, University of Wisconsin, Madison, Wisconsin, 53715, USA.

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.Caloric restriction has been shown to increase lifespan in mammals. Here, the authors provide evidence that age-related methylation drift correlates with lifespan and that caloric restriction in mice and rhesus monkeys results in attenuation of age-related methylation drift.

PMID:
28912502
PMCID:
PMC5599616
DOI:
10.1038/s41467-017-00607-3
[Indexed for MEDLINE]
Free PMC Article

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