Epigenetic-mediated decline in synaptic plasticity during aging

Rejuvenation Res. 2012 Feb;15(1):98-101. doi: 10.1089/rej.2012.1312.

Abstract

Cognitive decline observed in aging mammals is associated with decreased long-term synaptic plasticity, especially long-term potentiation (LTP). Recent work has uncovered a connection between LTP, histone acetylation, and brain-derived neurotrophic factor (BDNF)/neurotrophin receptor B (trkB) signaling. LTP, histone acetylation, and BDNF/trkB signaling decrease in old animals, Because an apparent positive feedback loop links these processes, treatment with histone deacetylase inhibitors or a trkB agonist restores LTP in the hippocampus of old animals. These results coupled with exciting work on histone methylation and life span in Caneorhabditis elegans suggest that epigenetic changes may play a significant role in aging. Such dysfunctional epigenetic pathways may provide novel targets for cognitive enhancing therapeutics.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Aging*
  • Animals
  • Caenorhabditis elegans
  • Cognition Disorders / metabolism
  • Epigenesis, Genetic*
  • Hippocampus / metabolism
  • Histones / metabolism
  • Humans
  • Long-Term Potentiation
  • Longevity
  • Models, Animal
  • Neuronal Plasticity*
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism*
  • Synapses / metabolism*

Substances

  • Histones
  • Receptor, trkB