Calcium and neuronal ageing.

Brain ageing is associated with a marked decline in mental faculties. One hypothesis postulates that sustained changes in the regulation of intracellular Ca2+ concentration, [Ca2+]i, are the major cause of neuronal degeneration. This 'calcium hypothesis' is supported by demonstrations of the impairment in aged neurones of molecular cascades that regulate [Ca2+]i. However, the number of direct measurements of [Ca2+]i in senescent neurones is limited, and the hypothesis cannot be regarded as fully confirmed. Furthermore, physiological brain ageing, at least in certain regions, need not necessarily be a degenerative process accompanied by neuronal loss. Pharmacological manipulation of Ca2+ entry has been shown to be effective in increasing some aspects of cognitive function of the aged brain. Therefore, further exploration of Ca2+ homeostasis and signalling might reveal the mechanisms involved in the age-dependent decline in neuronal performance, and might aid the search for new therapeutic treatments.