Cellular and molecular correlates of aging in the nervous system

Three characteristic features of aging in the nervous system are reviewed: deficits in the regulation of nerve-cell calcium levels, increased leakage of synaptic transmitters and changes in neuronal arborization. In hippocampal cells and motor nerve terminals, the rate of calcium clearance from the immediate vicinity of the membrane decreases with age. There is further evidence of decreased rates of transmembrane Ca2+ flux in synaptosomal preparations from aged animals. Stimulation-evoked transmitter release, which is calcium dependent, appears to increase at some neuromuscular junctions during aging; in contrast, high-K+-induced release in brain tissue appears to decline. A much more consistent age-related increase in "basal" transmitter efflux, under nonstimulated conditions, has been observed in both the peripheral and the central nervous system. This may be related to increased nerve-terminal arborization, which occurs in actively used muscles during aging. Likewise, dendritic branching becomes more extensive with moderate age; at advanced age, though, branching decreases. Furthermore, motor nerve terminal branching also decreases with age in muscles subject to disuse. This variability among morphologic features during aging illustrates the need to standardize ages and preparations when comparing these types of data.