Epigenetic assimilation in the aging human brain

Gabriel Oh, Sasha Ebrahimi, Sun Chong Wang, Rene Cortese, Zachary A. Kaminsky, Irving I. Gottesman, James R. Burke, Brenda L. Plassman, Art Petronis

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Background: Epigenetic drift progressively increases variation in DNA modification profiles of aging cells, but the finale of such divergence remains elusive. In this study, we explored the dynamics of DNA modification and transcription in the later stages of human life. Results: We find that brain tissues of older individuals (>75 years) become more similar to each other, both epigenetically and transcriptionally, compared with younger individuals. Inter-individual epigenetic assimilation is concurrent with increasing similarity between the cerebral cortex and the cerebellum, which points to potential brain cell dedifferentiation. DNA modification analysis of twins affected with Alzheimer's disease reveals a potential for accelerated epigenetic assimilation in neurodegenerative disease. We also observe loss of boundaries and merging of neighboring DNA modification and transcriptomic domains over time. Conclusions: Age-dependent epigenetic divergence, paradoxically, changes to convergence in the later stages of life. The newly described phenomena of epigenetic assimilation and tissue dedifferentiation may help us better understand the molecular mechanisms of aging and the origins of diseases for which age is a risk factor.

Original languageEnglish
Article number76
JournalGenome Biology
Issue number1
StatePublished - 28 Apr 2016


  • Aging
  • Alzheimer's disease
  • DNA methylation
  • Dedifferentiation
  • Epigenetic drift
  • Epigenetics
  • Genomic organization
  • Transcriptome


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