PRC2-AgeIndex as a universal biomarker of aging and rejuvenation

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 Oord, Wanding Zhou, Andrew Smith, Crystal Mackall, Vadim N. Gladyshev, Steve Horvath, Michael P. Snyder () and Vittorio Sebastiano ()
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Andrea Cipriano: Stanford University
Daniel J. Simpson: Stanford University
Sajede Rasouli: Stanford University
Tara Murty: Stanford University
Tineke Anna Jong: 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
Vadim N. Gladyshev: Harvard Medical School
Steve Horvath: University of California
Michael P. Snyder: Stanford University
Vittorio Sebastiano: Stanford University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50098-2

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