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Nonlinear DNA methylation trajectories in aging male mice

Author

Listed:
  • Maja Olecka

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Alena Bömmel

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Lena Best

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Madlen Haase

    (Jena University Hospital)

  • Silke Foerste

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Konstantin Riege

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Thomas Dost

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Stefano Flor

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Otto W. Witte

    (Jena University Hospital)

  • Sören Franzenburg

    (Kiel University and University Medical Center Schleswig-Holstein)

  • Marco Groth

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Björn Eyss

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Christoph Kaleta

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Christiane Frahm

    (Jena University Hospital)

  • Steve Hoffmann

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

Abstract

Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigate the methylation trajectories of male mouse colon at five different time points of aging. Our study indicates the existence of sudden hypermethylation events at specific stages of life. Precisely, we identify two epigenomic switches during early-to-midlife (3-9 months) and mid-to-late-life (15-24 months) transitions, separating the rodents’ life into three stages. These nonlinear methylation dynamics predominantly affect genes associated with the nervous system and enrich in bivalently marked chromatin regions. Based on groups of nonlinearly modified loci, we construct a clock-like classifier STageR (STage of aging estimatoR) that accurately predicts murine epigenetic stage. We demonstrate the universality of our clock in an independent mouse cohort and with publicly available datasets.

Suggested Citation

  • Maja Olecka & Alena Bömmel & Lena Best & Madlen Haase & Silke Foerste & Konstantin Riege & Thomas Dost & Stefano Flor & Otto W. Witte & Sören Franzenburg & Marco Groth & Björn Eyss & Christoph Kaleta , 2024. "Nonlinear DNA methylation trajectories in aging male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47316-2
    DOI: 10.1038/s41467-024-47316-2
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