[PDF][PDF] Aging-dependent demethylation of regulatory elements correlates with chromatin state and improved β cell function

D Avrahami, C Li, J Zhang, J Schug, R Avrahami… - Cell metabolism, 2015 - cell.com
D Avrahami, C Li, J Zhang, J Schug, R Avrahami, S Rao, MB Stadler, L Burger, D Schübeler
Cell metabolism, 2015cell.com
Aging is driven by changes of the epigenetic state that are only partially understood. We
performed a comprehensive epigenomic analysis of the pancreatic β 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 β cells. Importantly, we discover
targeted changes in the methylation status of β cell proliferation and function genes that go
against the global methylation drift, are specific to β cells, and correlate with repression of …
Summary
Aging is driven by changes of the epigenetic state that are only partially understood. We performed a comprehensive epigenomic analysis of the pancreatic β 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 β cells. Importantly, we discover targeted changes in the methylation status of β cell proliferation and function genes that go against the global methylation drift, are specific to β 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 β cells. Strikingly, we find β 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.
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