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PRC2-AgeIndex as a universal biomarker of aging and rejuvenation

Author

Listed:
  • Mahdi Moqri

    (Stanford University
    Stanford University
    Harvard Medical School
    Stanford University)

  • Andrea Cipriano

    (Stanford University
    Stanford University)

  • Daniel J. Simpson

    (Stanford University
    Stanford University)

  • Sajede Rasouli

    (Stanford University
    Stanford University)

  • Tara Murty

    (Stanford University)

  • Tineke Anna Jong

    (Stanford University
    Stanford University)

  • Daniel Nachun

    (Stanford University)

  • Guilherme Sena Brandine

    (University of Southern California)

  • Kejun Ying

    (Harvard Medical School)

  • Andrei Tarkhov

    (Harvard Medical School)

  • Karolina A. Aberg

    (Virginia Commonwealth University)

  • Edwin Oord

    (Virginia Commonwealth University)

  • Wanding Zhou

    (The Children’s Hospital of Philadelphia)

  • Andrew Smith

    (University of Southern California)

  • Crystal Mackall

    (Stanford University
    Stanford University
    Stanford University)

  • Vadim N. Gladyshev

    (Harvard Medical School)

  • Steve Horvath

    (University of California
    Altos Labs)

  • Michael P. Snyder

    (Stanford University
    Stanford University)

  • Vittorio Sebastiano

    (Stanford University
    Stanford University
    Stanford University)

Abstract

DNA methylation (DNAm) is one of the most reliable biomarkers of aging across mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, DNAm gain is less characterized. Studies have demonstrated that CpGs which gain methylation with age are enriched in Polycomb Repressive Complex 2 (PRC2) targets. However, whole-genome examination of all PRC2 targets as well as determination of the pan-tissue or tissue-specific nature of these associations is lacking. Here, we show that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells (PRC2 LMRs) gain methylation with age in all examined somatic mitotic cells. We estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the “PRC2-AgeIndex,” defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells which can distinguish the effect of different anti-aging interventions.

Suggested Citation

  • Mahdi Moqri & Andrea Cipriano & Daniel J. Simpson & Sajede Rasouli & Tara Murty & Tineke Anna Jong & Daniel Nachun & Guilherme Sena Brandine & Kejun Ying & Andrei Tarkhov & Karolina A. Aberg & Edwin O, 2024. "PRC2-AgeIndex as a universal biomarker of aging and rejuvenation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50098-2
    DOI: 10.1038/s41467-024-50098-2
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    References listed on IDEAS

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