The idea that age-related cognitive decline is associated with disruption of calcium (Ca2+) homeostasis has been investigated over the past two decades. Much of this work has focused on the hippocampus because hippocampal-dependent memory is age sensitive. It is now well established that Ca2+-dependent processes such as susceptibility to neurotoxicity, the afterhyperpolarization amplitude, induction of synaptic plasticity, and long-term potentiation and long-term depression are altered with age. Recent work has identified changes in Ca2+signaling pathways that may underlie the development of these biological markers of aging. This review considers recent findings concerning interactions between the various Ca2+-dependent processes, with special emphasis on the role of altered Ca2+ regulation and disruption of Ca2+ signaling pathways in mediating the expression of biological and behavioral markers of brain aging.
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