Calcium homeostasis and modulation of synaptic plasticity in the aged brain

Aging Cell. 2007 Jun;6(3):319-25. doi: 10.1111/j.1474-9726.2007.00283.x.


The level of intracellular Ca2+ plays a central role in normal and pathological signaling within and between neurons. These processes involve a cascade of events for locally raising and lowering cytosolic Ca2+. As the mechanisms for age-related alteration in Ca2+ dysregulation have been illuminated, hypotheses concerning Ca2+ homeostasis and brain aging have been modified. The idea that senescence is due to pervasive cell loss associated with elevated resting Ca2+ has been replaced by concepts concerning changes in local Ca2+ levels associated with neural activity. This article reviews evidence for a shift in the sources of intracellular Ca2+ characterized by a diminished role for N-methyl-D-aspartate receptors and an increased role for intracellular stores and voltage-dependent Ca2+ channels. Physiological and biological models are outlined, which relate a shift in Ca2+ regulation with changes in cell excitability and synaptic plasticity, resulting in a functional lesion of the hippocampus.

Publication types

  • Review

MeSH terms

  • Aged
  • Aging*
  • Animals
  • Brain / metabolism*
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Homeostasis*
  • Humans
  • Models, Biological
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neuronal Plasticity*
  • Neurons / metabolism
  • Oxidative Stress
  • Signal Transduction
  • Synapses / physiology*


  • Calcium Channels
  • Calcium