Abstract:
: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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Avrahami D,Li C,Zhang J,Schug J,Avrahami R,Rao S,Stadler MB,Burger L,Schübeler D,Glaser B,Kaestner KHdoi
10.1016/j.cmet.2015.07.025subject
Has Abstractpub_date
2015-10-06 00:00:00pages
619-32issue
4eissn
1550-4131issn
1932-7420pii
S1550-4131(15)00388-5journal_volume
22pub_type
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