PRC2-AgeIndex as a universal biomarker of aging and rejuvenation

被引：15

作者：

Moqri, Mahdi ^{[1
,2
,3
,4
]}

Cipriano, Andrea ^{[2
,5
]}

Simpson, Daniel J. ^{[2
,5
]}

Rasouli, Sajede ^{[2
,5
]}

Murty, Tara ^{[6
]}

de Jong, Tineke Anna ^{[2
,5
]}

Nachun, Daniel ^{[7
]}

Brandine, Guilherme de Sena ^{[8
]}

Ying, Kejun ^{[3
]}

Tarkhov, Andrei ^{[3
]}

Aberg, Karolina A. ^{[9
]}

van den Oord, Edwin ^{[9
]}

Zhou, Wanding ^{[10
]}

Smith, Andrew ^{[8
]}

Mackall, Crystal ^{[6
,11
,12
]}

Gladyshev, Vadim N. ^{[3
]}

Horvath, Steve ^{[13
,14
]}

Snyder, Michael P. ^{[4
,15
]}

Sebastiano, Vittorio ^{[2
,5
,16
]}

机构：

[1] Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA USA

[2] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA

[4] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[6] Stanford Univ, Stanford Canc Inst, Ctr Canc Cell Therapy, Sch Med, Stanford, CA USA

[7] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA USA

[8] Univ Southern Calif, Quantitat & Computat Biol, Los Angeles, CA USA

[9] Virginia Commonwealth Univ, Ctr Biomarker Res & Precis Med, Richmond, VA 23298 USA

[10] Childrens Hosp Philadelphia, Ctr Computat & Genom Med, Philadelphia, PA USA

[11] Stanford Univ, Sch Med, Dept Pediat, Div Hematol & Oncol, Stanford, CA USA

[12] Stanford Univ, Sch Med, Dept Med, Div Stem Cell Transplantat & Cell Therapy, Stanford, CA USA

[13] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA USA

[14] Altos Labs, San Diego, CA USA

[15] Stanford Univ, Ctr Genom & Personalized Med, Stanford, CA 94305 USA

[16] Stanford Univ, Stanford Maternal & Child Hlth Res Inst, Stanford, CA 94305 USA

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

DNA METHYLATION; BIOLOGICAL AGE; HYPERMETHYLATION; PROLIFERATION; SIGNATURE; PATTERN; GENES;

D O I：

10.1038/s41467-024-50098-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. DNA methylation (DNAm) is a key biomarker of aging, with age-related DNAm changes being well-characterized. Here, the authors show that low-methylated regions (LMRs) bound by PRC2 in embryonic stem cells gain methylation with age in somatic cells, proposing the "PRC2-AgeIndex" as a universal biomarker of cellular aging.

引用

页数：12

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