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The Neurobiology of Cerebellar Senescence

Mechanisms of neural senescence have been intensely pursued, but any kind of fundamental understanding remains elusive.' The difficulty is not in finding significant effects of age in the nervous system, but rather arises from the fact that aging is as ubiquitous in brain as it is in phylogeny: age changes can be detected at practically any level of analysis, from the molecular biology of ribosomes to the neuropsychology of cognition.2 Faced with this plethora of effects, perhaps the most difficult challenge facing those who study neural aging is the determination of which phenomena are primary, which are secondary, which are important, and which are only trivial epiphenomena. Because the cerebellum is one of the most extensively studied, best understood, and accessible structures in brain,3-'0 our laboratory has used it as a model system in which to characterize age changes in brain microanatomy,11-'6 physiology, 11-15 and function." Based on these results, a primary cytoarchitectural mechanismthe differential loss of specific terminal areas on the dendrite arbor of large output neurons, and the relative preservation of other terminal areas on these neurons is hypothesized to account for many of the physiologic and functional alterations that characterize the senescent cerebellum. A hypothesis such as this may generalize to other structures that, like the cerebellum, depend on highly arborized, long projecting, large diameter neurons for the final output of information processing.