Over the course of a human lifespan, genome integrity erodes, leading to an increased abundance of several types of chromatin changes. The abundance of DNA lesions (chemical perturbations to nucleotides) increases with age, as does the number of genomic mutations and transcriptional disruptions caused by replication or transcription of those lesions, respectively. At the epigenetic level, precise DNA methylation patterns degrade, likely causing increasingly stochastic variations in gene expression. Similarly, the tight regulation of histone modifications begins to unravel. The genomic instability caused by these mechanisms allows transposon element reactivation and remobilization, further mutations, gene dysregulation, and cytoplasmic chromatin fragments. This cumulative genomic instability promotes cell signaling events that drive cell fate decisions and extracellular communications known to disrupt tissue homeostasis and regeneration. In this Review, we focus on age-related epigenetic changes and their interactions with age-related genomic changes that instigate these events.

Original languageEnglish (US)
Article numbere158446
JournalJournal of Clinical Investigation
Issue number16
StatePublished - Aug 15 2022

Bibliographical note

Funding Information:
This work is supported by the NIH (R00-AG056656 to XD; R01-AG063543, ES029603, U19-AG056278, P01-AG062413, and U54-AG076041 to LJN), as well as the Impetus Grant, Norn Foundation; College of Food, Agricultural and Natural Resource Sciences Bridge Funding; and US Department of Agriculture–National Institute of Food and Agriculture MIN-16-129 to CDF.

Publisher Copyright:
© 2022 Soto-Palma et al.

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.


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