Parameters of calcium homeostasis in normal neuronal ageing

The last decade has witnessed a significant turn in our understanding of th e mechanisms responsible for the decline of cognitive functions in aged bra in. As has been demonstrated by detailed morphological reassessments, the s enescence-related changes in cognition cannot be attributed to a simple dec rease in the number of neurons. It is becoming clearer that a major cause o f age-induced deterioration of brain capability involves much subtler chang es at the level of synapses. These changes are either morphological, i.e. r eduction in the number of effective synapses and/or functional alterations, i.e. changes in the efficacy of remaining synapses. Important questions ar e now raised regarding the mechanisms which mediate these synaptic changes. Clearly, an important candidate is calcium, the cytotoxic role of which is already firmly established. The wealth of evidence collected so far regard ing the changes of Ca2+ homeostasis in aged neurons shows that the overall duration of cytoplasmic Ca2+ signals becomes longer. This is the most consi stent result, demonstrated on different preparations and using different te chniques. What is not yet clear is the underlying mechanism, as this result could be explained either through an increased Ca2+ influx or because of a deficit in the Ca2+ buffering/clearance systems. It is conceivable that th ese prolonged Ca2+ signals may exert a local excitotoxic effect, removing p referentially the most active synapses. Uncovering of the role of Ca2+ in t he synaptic function of the aged brain presents an exciting challenge for a ll those involved in the neurobiology of the senescent CNS.