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Methylated DNA Immunoprecipitation
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A whole lifespan mouse multi-tissue DNA methylation clock.

Margarita V Meer1, Dmitriy I Podolskiy1, Alexander Tyshkovskiy1,2

  • 1Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, United States.

Elife
|November 15, 2018
PubMed
Summary

Researchers developed a new mouse DNA methylation clock (DNAm clock) using 435 CpG sites. This robust, multi-tissue predictor accurately measures age across the entire lifespan and detects aging interventions.

Keywords:
DNA methylationagingbiological agechromosomesclockgene expressionlifespanmouse

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Area of Science:

  • Epigenetics and aging research
  • Mammalian aging studies
  • Biomarker development for aging

Background:

  • DNA methylation clocks (DNAm clocks) are established human aging predictors.
  • Existing mouse DNAm clocks have limitations, being tissue-specific or focused on young ages.
  • A need exists for a comprehensive mouse aging biomarker.

Purpose of the Study:

  • To develop a robust, multi-tissue DNA methylation clock for mice.
  • To create an age predictor that covers the entire mouse lifespan.
  • To assess the utility of DNAm clocks in aging and rejuvenation studies.

Main Methods:

  • Construction of a multi-tissue mouse DNAm clock using 435 CpG sites.
  • Validation of the clock across the entire mouse lifespan.
  • Testing the clock's ability to detect lifespan interventions and cellular reprogramming effects.

Main Results:

  • A novel mouse DNAm clock was developed, applicable across all ages and tissues.
  • The clock successfully identified effects of lifespan-modulating interventions.
  • The clock detected age reversal during the fibroblast to induced pluripotent stem cell (iPSC) transition.
  • Comparative analysis revealed strengths and weaknesses of existing mouse DNAm clocks.

Conclusions:

  • The new multi-tissue mouse DNAm clock is a valuable tool for aging research.
  • This predictor overcomes limitations of previous tissue-specific and age-biased clocks.
  • The developed clock aids in studying aging, interventions, and rejuvenation in mice.