title: Multi-tissue DNA methylation age predictor in mouse.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stubbs
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, UK.
authors.forename: Marc Jan
authors.initials: MJ
authors.lastname: Bonder
authors.affiliation: Immunology Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Anne-Katrien
authors.initials: AK
authors.lastname: Stark
authors.affiliation: Bioinformatics Group, The Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Felix
authors.initials: F
authors.lastname: Krueger
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK. vonmeyenn@babraham.ac.uk.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Meyenn
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, UK. oliver.stegle@ebi.ac.uk.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stegle
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK. wolf.reik@babraham.ac.uk.|Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK. wolf.reik@babraham.ac.uk.|Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK. wolf.reik@babraham.ac.uk.
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D009928:Organ Specificity / Q000235:genetics
keywords: Ageing/aging; Biological age; Chronological age; DNA methylation; Epigenetic clock; Epigenetics; High fat diet; Model; Ovariectomy; Prediction