TY - JOUR T1 - Multi-tissue DNA methylation age predictor in mouse JF - bioRxiv DO - 10.1101/119206 SP - 119206 AU - Thomas M. Stubbs AU - Marc Jan Bonder AU - Anne-Katrien Stark AU - Felix Krueger AU - Clock Team BI Ageing AU - Ferdinand von Meyenn AU - Oliver Stegle AU - Wolf Reik Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/22/119206.abstract N2 - 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 and 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 offspring diet.Conclusions Here we identify and characterize 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.RRBSReduced Representation Bisulphite SequencingWGBSWhole Genome Bisulphite SequencingGOGene OntologyPCAPrincipal Component AnalysisMAEMedian Absolute ErrorCGICpG Island ER -