The neurobiology of aging.

ABSTRACT

Basic principles of the neurobiology of aging were reviewed within selected topic areas chosen for their potential relevance to epileptogenesis in the aging brain. The availability of National Institute on Aging-supported aged mouse and rat strains and other biological resources for studies of aging and age-associated diseases was presented, and general principles of animal use in gerontological research were discussed. Neurobiological changes during normal brain aging were compared and contrasted with neuropathological events of Alzheimer's disease (AD) and age-associated memory impairment (AAMI). Major themes addressed were the loss of synaptic connections as vulnerable neurons die and circuits deteriorate in AD, the absence of significant neuron loss but potential synaptic alteration in the same circuits in AAMI, and the effects of decreased estrogen on normal aging. The "calcium hypothesis of brain aging" was examined by a review of calcium dyshomeostasis and synaptic communication in aged hippocampus, with particular emphasis on the role of L-type voltage-gated calcium channels during normal aging. Established and potential mechanisms of hippocampal plasticity during aging were discussed, including long-term potentiation, changes in functional connectivity, and increased gap junctions, the latter possibly being related to enhanced network excitability. Lastly, application of microarray gene chip technology to aging brain studies was presented and use of the hippocampal "zipper slice" preparation to study aged neurons was described.