Revisiting the genomic hypomethylation hypothesis of aging

Archana Unnikrishnan, Niran Hadad, Dustin R. Masser, Jordan Jackson, Willard M. Freeman, Arlan Richardson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans.We critically reviewed the publications on the effect of age on DNAmethylation and the expression of the enzymes involved in DNAmethylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age-related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - 2018


  • Aging
  • DNA methylation
  • DNA methylation enzymes
  • Dietary restriction
  • Gene expression
  • Hypomethylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science


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