Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction

Summary Aging is characterized by numerous molecular changes, such as accumulation of molecular damage and altered gene expression, many of which are linked to DNA methylation. Here, we characterize the blood DNA methylome across 16 age groups of mice and report numerous global, region‐ and site‐spe...

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Bibliographic Details
Published in:Aging cell Vol. 17; no. 3; pp. e12738 - n/a
Main Authors: Sziráki, András, Tyshkovskiy, Alexander, Gladyshev, Vadim N.
Format: Journal Article
Language:English
Published: England John Wiley & Sons, Inc 01.06.2018
John Wiley and Sons Inc
Subjects:
Age
Aging
Aging - genetics
Animals
Caloric Restriction - methods
calorie restriction
Deoxyribonucleic acid
DNA
DNA - genetics
DNA methylation
DNA Methylation - genetics
Entropy
Gene expression
Genes
Life span
Methylation
Mice
Nutrient deficiency
Original
DNA methylation
calorie restriction
entropy
aging
ISSN:1474-9718, 1474-9726, 1474-9726
Online Access:Get full text
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Summary:Summary Aging is characterized by numerous molecular changes, such as accumulation of molecular damage and altered gene expression, many of which are linked to DNA methylation. Here, we characterize the blood DNA methylome across 16 age groups of mice and report numerous global, region‐ and site‐specific features, as well as the associated dynamics of methylation changes. Transition of the methylome throughout lifespan was not uniform, with many sites showing accelerated changes in late life. The associated genes and promoters were enriched for aging‐related pathways, pointing to a fundamental link between DNA methylation and control of the aging process. Calorie restriction both shifted the overall methylation pattern and was accompanied by its gradual age‐related remodeling, the latter contributing to the lifespan‐extending effect. With age, both highly and poorly methylated sites trended toward intermediate levels, and aging was accompanied by an accelerated increase in entropy, consistent with damage accumulation. However, the entropy effects differed for the sites that increased, decreased and did not change methylation with age. Many sites trailed behind, whereas some followed or even exceeded the entropy trajectory and altered the developmental DNA methylation pattern. The patterns we observed in certain genomic regions were conserved between humans and mice, suggesting common principles of functional DNA methylome remodeling and its critical role in aging. The highly resolved DNA methylome remodeling provides an excellent model for understanding systemic changes that characterize the aging process.
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ISSN:1474-9718
1474-9726
1474-9726
DOI:10.1111/acel.12738