Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities

Nat Neurosci. 2012 Jul 1;15(8):1111-3. doi: 10.1038/nn.3151.


Cognitive abilities decline in normal aging, yet the underlying molecular mechanisms are poorly understood. We found that aging was associated with a decrease in the expression of the DNA methyltransferase Dnmt3a2 in the hippocampus and that rescuing Dnmt3a2 levels restored cognitive functions. Moreover, we found that Dnmt3a2 is an activity-regulated immediate early gene that is partly dependent on nuclear calcium signaling and that hippocampal Dnmt3a2 levels determine cognitive abilities in both young adult and aged mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / psychology
  • Animals
  • Cognition / physiology*
  • Cognition Disorders / enzymology*
  • DNA (Cytosine-5-)-Methyltransferases / biosynthesis*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / physiology
  • DNA Methylation / physiology
  • Hippocampus / enzymology*
  • Memory Disorders / enzymology
  • Memory, Long-Term / physiology
  • Mice


  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3A