PRC2-AgeIndex as a universal biomarker of aging and rejuvenation

Mahdi Moqri; Andrea Cipriano; Daniel J. Simpson; Sajede Rasouli; Tara Murty; Tineke Anna de Jong; Daniel Nachun; Guilherme de Sena Brandine; Kejun Ying; Andrei Tarkhov; Karolina A. Aberg; Edwin van den Oord; Wanding Zhou; Andrew Smith; Crystal Mackall; Vadim N. Gladyshev; Steve Horvath; Michael P. Snyder; Vittorio Sebastiano

doi:10.1038/s41467-024-50098-2

Nature Communications (Jul 2024)

PRC2-AgeIndex as a universal biomarker of aging and rejuvenation

Mahdi Moqri,
Andrea Cipriano,
Daniel J. Simpson,
Sajede Rasouli,
Tara Murty,
Tineke Anna de Jong,
Daniel Nachun,
Guilherme de Sena Brandine,
Kejun Ying,
Andrei Tarkhov,
Karolina A. Aberg,
Edwin van den Oord,
Wanding Zhou,
Andrew Smith,
Crystal Mackall,
Vadim N. Gladyshev,
Steve Horvath,
Michael P. Snyder,
Vittorio Sebastiano

Affiliations

Mahdi Moqri: Department of Biomedical Data Science, School of Medicine, Stanford University
Andrea Cipriano: Department of Obstetrics & Gynecology, School of Medicine, Stanford University
Daniel J. Simpson: Department of Obstetrics & Gynecology, School of Medicine, Stanford University
Sajede Rasouli: Department of Obstetrics & Gynecology, School of Medicine, Stanford University
Tara Murty: Center for Cancer Cell Therapy, Stanford Cancer Institute, School of Medicine, Stanford University
Tineke Anna de Jong: Department of Obstetrics & Gynecology, School of Medicine, Stanford University
Daniel Nachun: Department of Pathology, School of Medicine, Stanford University
Guilherme de Sena Brandine: Quantitative and Computational Biology, University of Southern California
Kejun Ying: Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Andrei Tarkhov: Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Karolina A. Aberg: Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University
Edwin van den Oord: Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University
Wanding Zhou: Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia
Andrew Smith: Quantitative and Computational Biology, University of Southern California
Crystal Mackall: Center for Cancer Cell Therapy, Stanford Cancer Institute, School of Medicine, Stanford University
Vadim N. Gladyshev: Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Steve Horvath: Department of Human Genetics, David Geffen School of Medicine, University of California
Michael P. Snyder: Department of Genetics, School of Medicine, Stanford University
Vittorio Sebastiano: Department of Obstetrics & Gynecology, School of Medicine, Stanford University

DOI: https://doi.org/10.1038/s41467-024-50098-2
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 12

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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