AI Article Synopsis

  • Aging affects the epigenetic state of pancreatic β cells, leading to global changes in DNA methylation as mice age.
  • Despite a general trend of less methylation in old β cells, specific genes related to cell proliferation and function show unique methylation changes that counter this trend.
  • Remarkably, the findings suggest that aged β cells in mice may have improved function, indicating that aging does not necessarily result in decreased performance of these cells.

Article 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598285PMC
http://dx.doi.org/10.1016/j.cmet.2015.07.025DOI Listing

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