TY - JOUR
T1 - Caloric restriction delays age-related methylation drift
AU - Maegawa, Shinji
AU - Lu, Yue
AU - Tahara, Tomomitsu
AU - Lee, Justin T.
AU - Madzo, Jozef
AU - Liang, Shoudan
AU - Jelinek, Jaroslav
AU - Colman, Ricki J.
AU - Issa, Jean Pierre J.
N1 - Funding Information:
The high-throughput sequencing was supported by Core grant CA016672 (SMF) to The University of Texas MD Anderson Cancer Center. The Genomic Facility at Fox Chase Cancer Center was supported by Core Grant CA006927 to the Fox Chase Cancer Center. This work was supported by National Institutes of Health grants CA158112 (to J.-P.J.I.) and NIH/NIA grants AG11915, and AG040178 (to R.J.C.) and by a grant from the Ellison Medical Foundation (to J.-P.J.I.). Research reported in this publication was supported in part by the Office of the Director, National Institutes of Health under Award Number P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. J.-P.J.I. is an American Cancer Society Clinical Research professor supported by a generous gift from the F. M. Kirby Foundation.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-00607-3
DO - 10.1038/s41467-017-00607-3
M3 - Article
C2 - 28912502
AN - SCOPUS:85029494791
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 539
ER -