Changes in calcium's role as a messenger during aging in neuronal and nonneuronal cells.
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.
Peterson
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Division of Neurobiology, University of Southern California, Los Angeles 90089-0191.
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016922:Cellular Senescence; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism; D015290:Second Messenger Systems
D002135:Calcium-Binding Proteins; D017470:Receptors, Glutamate; D002118:Calcium