Alterations in
calcium transport appear to be functionally significant. Treatment with drugs that promote
calcium uptake partially reverse some of the age-related deficits in
calcium-dependent processes. Thus, the relevance of decreased
calcium coupled receptor binding is supported by the ability of
3,4-diaminopyridine to promote
acetylcholine release by forebrain slices from aged mice. This
drug also reduces the age-related depression in synaptosomal
calcium uptake in aged rats and mice.
3,4-Diaminopyridine also reverses the age-related deficit in
calcium transport, the age-related deficits in the tight rope test, and 8 arm maze performance.
3,4-Diaminopyridine is also effective in nonexcitable tissues, such as cultured skin fibroblasts; it increases the decreased cytosolic-free
calcium. Depressed cell spreading of fibroblasts can be reversed by treatment of cells with the
calcium ionophore A23187 which promotes
calcium influx.
4-Aminopyridine, a similarly related compound, partially reverses short-term memory deficits in patients with
Alzheimer's disease.
Tetrahydroaminoacridine, an
aminopyridine analog with
anticholinesterase properties, produces clinical improvement in behavioral deficits due to
Alzheimer's disease. Only recently has the aging brain become a subject of intense study. Evidently, the neurobiology of aging needs to develop its own theories to account for the unique aspects of brain aging as well as integrate them with the peripheral changes. An exciting but unexplored area of research in the aging brain concerns the coupling between
calcium and the final end product, the induction of genes. Still unknown are the molecular events that set these processes in motion. In addition, whether conditions such as
dietary restriction that increase longevity in certain rodents also retard age-related changes in
calcium remains to be determined.