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Multi-tissue DNA methylation age predictor in mouse.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Stubbs, Thomas M 
Bonder, Marc Jan 
Stark, Anne-Katrien 
Krueger, Felix 
BI Ageing Clock Team 

Abstract

BACKGROUND: DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. RESULTS: We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop a multi-tissue predictor of age in the mouse. Our model, which estimates age based on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouse clock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results in significant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet. CONCLUSIONS: Here we identify and characterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageing and will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.

Description

Keywords

Ageing/aging, Biological age, Chronological age, DNA methylation, Epigenetic clock, Epigenetics, High fat diet, Model, Ovariectomy, Prediction, Aging, Animals, Cluster Analysis, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Profiling, Humans, Male, Mice, Organ Specificity

Journal Title

Genome Biol

Conference Name

Journal ISSN

1474-7596
1474-760X

Volume Title

18

Publisher

Springer Science and Business Media LLC
Sponsorship
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0405)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0404)