Aging-Dependent Demethylation of Regulatory Elements Correlates with Chromatin State and Improved β Cell Function

被引：160

作者：

Avrahami, Dana ^{[1
,2
,5
]}

Li, Changhong ^{[3
]}

Zhang, Jia ^{[1
,2
]}

Schug, Jonathan ^{[1
,2
]}

Avrahami, Ran ^{[1
,2
]}

Rao, Shilpa ^{[1
,2
]}

Stadler, Michael B. ^{[4
]}

Burger, Lukas ^{[4
]}

Schuebeler, Dirk ^{[4
]}

Glaser, Benjamin ^{[5
]}

Kaestner, Klaus H. ^{[1
,2
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA

[4] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[5] Hebrew Univ Jerusalem, Hadassah Med Ctr, Endocrinol & Metab Serv, IL-91120 Jerusalem, Israel

来源：

CELL METABOLISM | 2015年 / 22卷 / 04期

关键词：

MASS; PROLIFERATION; ADAPTATION; ENHANCERS; EXPANSION; ISLETS; LOCUS; AGE;

D O I：

10.1016/j.cmet.2015.07.025

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Aging is driven by changes of the epigenetic state that are only partially understood. We performed a comprehensive epigenomic analysis of the pancreatic beta cell, key player in glucose homeostasis, in adolescent and very old mice. We observe a global methylation drift resulting in an overall more leveled methylome in old b cells. Importantly, we discover targeted changes in the methylation status of b cell proliferation and function genes that go against the global methylation drift, are specific to b cells, and correlate with repression of the proliferation program and activation of metabolic regulators. These targeted alterations are associated with specific chromatin marks and transcription factor occupancy in young b cells. Strikingly, we find b cell function improved in aged mice, as predicted by the changes in methylome and transcriptome. Thus, aging of terminally differentiated cells in mammals is not always coupled to functional decline.

引用

页码：619 / 632

页数：14

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