PT  - JOURNAL ARTICLE
AU  - Mahdi Moqri
AU  - Andrea Cipriano
AU  - Daniel Nachun
AU  - Tara Murty
AU  - Guilherme de Sena Brandine
AU  - Sajede Rasouli
AU  - Andrei Tarkhov
AU  - Karolina A. Aberg
AU  - Edwin van den Oord
AU  - Wanding Zhou
AU  - Andrew Smith
AU  - Crystal Mackall
AU  - Vadim Gladyshev
AU  - Steve Horvath
AU  - Michael P. Snyder
AU  - Vittorio Sebastiano
TI  - PRC2 clock: a universal epigenetic biomarker of aging and rejuvenation
AID  - 10.1101/2022.06.03.494609
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.03.494609
4099  - http://biorxiv.org/content/early/2022/06/05/2022.06.03.494609.short
4100  - http://biorxiv.org/content/early/2022/06/05/2022.06.03.494609.full
AB  - DNA methylation (DNAm) is one of the most reliable biomarkers for aging across many mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, age-dependent DNAm gain is less specified. Multiple studies have demonstrated that polycomb repressive complex 2 (PRC2) targets are enriched among the CpG sites which gain methylation with age. However, a systematic whole-genome examination of all PRC2 targets in the context of aging methylome as well as whether these associations are pan-tissue or tissue-specific is lacking. Here, by analyzing DNAm data from different assays and from multiple young and old human and mouse tissues, we found that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells gain methylation with age in all examined somatic mitotic cells. We also estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the “PRC2 clock,” defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells. In addition, we demonstrate the application of this biomarker in the evaluation of different anti-aging interventions, including dietary restriction and partial epigenetic reprogramming.Competing Interest StatementV.S. is a co-founder, SAB Chairman and shareholders of Turn Biotechnologies. SH is a founder of the non-profit Epigenetic Clock Development Foundation