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Related Experiment Video

Updated: Aug 26, 2025

Reusable Single Cell for Iterative Epigenomic Analyses
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Reusable Single Cell for Iterative Epigenomic Analyses

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Profiling epigenetic age in single cells.

Alexandre Trapp1, Csaba Kerepesi1, Vadim N Gladyshev1

  • 1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Nature Aging
|October 10, 2022
PubMed
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We developed scAge, a new method to measure biological age in single cells using DNA methylation. This framework tracks aging in various cell types and reveals rejuvenation events during development.

Area of Science:

  • Epigenetics
  • Genomics
  • Computational Biology

Background:

  • DNA methylation is a key biomarker for mammalian aging.
  • Multivariate machine learning models, known as epigenetic clocks, measure biological age in bulk tissues.
  • Assessing aging in single-cell data has been challenging due to sparse methylation profiles.

Purpose of the Study:

  • Introduce scAge, a statistical framework for epigenetic age profiling at single-cell resolution.
  • Validate the scAge approach in mouse models.
  • Enable exploration of epigenetic aging trajectories at the single-cell level.

Main Methods:

  • Developed a novel statistical framework, scAge, for single-cell epigenetic age estimation.
  • Applied scAge to mouse tissues, including hepatocytes, muscle stem cells, and embryonic stem cells.

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  • Validated scAge's ability to recapitulate chronological age and reveal cellular heterogeneity.
  • Main Results:

    • scAge accurately recapitulates chronological age in various cell types.
    • Identified attenuated epigenetic aging in muscle stem cells.
    • Tracked age dynamics in hepatocytes and embryonic stem cells.
    • Revealed a natural, stratified rejuvenation event during early embryogenesis at the single-cell level.

    Conclusions:

    • scAge provides a powerful tool for single-cell epigenetic age profiling.
    • The framework uncovers cellular heterogeneity in aging processes.
    • scAge facilitates the study of aging and rejuvenation dynamics at unprecedented resolution.