Synaptic Function and Behavior During Normal Ageing

Abstract

During normal aging of the brain there is very little loss of nerve cells in most brain regions despite the fact that there is typically impaired function of a number of systems including those involved in learning and memory and motor function. It is increasingly recognized that age-related changes in the molecular composition and structure and function of synapses contributes greatly to changes in brain function during normal aging. In this special issue of the journal authors describe age-related changes that occur in synapses and behavior during normal aging. These include biophysical alterations in the regulation of ion fluxes across synaptic membranes and associated changes in synaptic plasticity that likely underlie age-related impairments in cognitive function. The signal transduction pathways involved in synaptic plasticity, how they are affected by the aging process and ways in which these changes might be delayed or prevented are described. In particular, environmental factors are increasingly recognized as being capable of modulating age-related alterations in synaptic functions and behavior. Examples include: cognitive stimulation, physical exercise and dietary restriction, all of which promote maintained function during aging. Neurotrophic factors such as BDNF appear to be particularly important in regulating plasticity during aging. Finally, research in this field is moving towards establishing ways of preventing synaptic dysfunction or replacing lost neurons and synapses in aging and age-related neurodegenerative disorders. This issue of ARR provides the reader with an integrated view of the kinds of cellular, molecular and environmental factors that underlie both normal and abnormal brain aging in relation to synaptic function. The processes that may contribute to synaptic dysfunction during aging must also be seen in the wider context of the age-related changes in normal neuronal physiology, including oxidative stress, impaired energy metabolism and dysregulation of cellular calcium homeostasis. These issues have been discussed in a recent special issue of Trends in Neurosciences (October, 2004), to which the interested reader is referred.