A whole lifespan mouse multi-tissue DNA methylation clock

Elife. 2018 Nov 14:7:e40675. doi: 10.7554/eLife.40675.

Abstract

Age predictors based on DNA methylation levels at a small set of CpG sites, DNAm clocks, have been developed for humans and extended to several other species. Three currently available versions of mouse DNAm clocks were either created for individual tissues or tuned toward young ages. Here, we constructed a robust multi-tissue age predictor based on 435 CpG sites, which covers the entire mouse lifespan and remains unbiased with respect to any particular age group. It can successfully detect the effects of certain lifespan-modulating interventions on DNAm age as well as the rejuvenation effect related to the transition from fibroblasts to iPSCs. We have carried out comparative analyses of available mouse DNAm clocks, which revealed their broad applicability, but also certain limitations to the use of tissue-specific and multi-tissue age predictors. Together, these tools should help address diverse questions in aging research.

Keywords: DNA methylation; aging; biological age; chromosomes; clock; gene expression; lifespan; mouse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Animals
  • CpG Islands
  • DNA / genetics*
  • DNA / metabolism
  • DNA Methylation*
  • Datasets as Topic
  • Epigenesis, Genetic*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Hippocampus / chemistry
  • Hippocampus / metabolism
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Liver / chemistry
  • Liver / metabolism
  • Longevity / genetics*
  • Lung / chemistry
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Myocardium / chemistry
  • Myocardium / metabolism
  • Organ Specificity
  • Rejuvenation / physiology

Substances

  • DNA