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

PRC2-AgeIndex as a universal biomarker of aging and rejuvenation

Nat Commun. 2024 Jul 16;15(1):5956. doi: 10.1038/s41467-024-50098-2.

Authors

Mahdi Moqri^#^{1

2

3

4}, Andrea Cipriano^#^{2

5}, Daniel J Simpson^#^{2

5}, Sajede Rasouli^{2

5}, Tara Murty⁶, Tineke Anna de Jong^{2

5}, Daniel Nachun⁷, Guilherme de Sena Brandine⁸, Kejun Ying³, Andrei Tarkhov³, Karolina A Aberg⁹, Edwin van den Oord⁹, Wanding Zhou¹⁰, Andrew Smith⁸, Crystal Mackall^{6

11

12}, Vadim N Gladyshev³, Steve Horvath^{13

14}, Michael P Snyder^{15

16}, Vittorio Sebastiano^{17

18

19}

Affiliations

¹ Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, USA.
² Department of Obstetrics & Gynecology, School of Medicine, Stanford University, Stanford, CA, USA.
³ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
⁵ Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
⁶ Center for Cancer Cell Therapy, Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
⁷ Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
⁸ Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA.
⁹ Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
¹⁰ Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹¹ Department of Pediatrics, Division of Hematology and Oncology, School of Medicine, Stanford University, Stanford, CA, USA.
¹² Department of Medicine, Division of Stem Cell Transplantation and Cell Therapy, School of Medicine, Stanford University, Stanford, CA, USA.
¹³ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
¹⁴ Altos Labs, San Diego, CA, USA.
¹⁵ Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA. [email protected].
¹⁶ Center for Genomics and Personalized Medicine, Stanford University, Stanford, CA, USA. [email protected].
¹⁷ Department of Obstetrics & Gynecology, School of Medicine, Stanford University, Stanford, CA, USA. [email protected].
¹⁸ Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA, USA. [email protected].
¹⁹ Stanford Maternal & Child Health Research Institute, Stanford University, Stanford, CA, USA. [email protected].

^# Contributed equally.

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.

MeSH terms

Aging* / genetics
Aging* / metabolism
Animals
Biomarkers* / metabolism
Cellular Senescence / genetics
CpG Islands
DNA Methylation*
Embryonic Stem Cells / metabolism
Epigenesis, Genetic*
Female
Humans
Male
Mice
Polycomb Repressive Complex 2* / genetics
Polycomb Repressive Complex 2* / metabolism
Rejuvenation* / physiology

Substances

Polycomb Repressive Complex 2
Biomarkers

Abstract

MeSH terms

Substances

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