DEFICITS IN LEARNING AND MEMORY THAT OCCUR WITH AGING 
Experimental work with animals has had unique advantages in studying fundamental 
biological processes affecting cognitive behavior during the latter stages of aging. Because 
many animals age much more rapidly than humans (e.g., rats age approximately 30 times as 
fast as humans) experimental work with laboratory animals has enabled researchers to 
perform studies that would take decades or generations to conduct if limited to human 
subjects. 
Experimental studies on a number of different species of aged laboratory animals have shown 
similarities in learning and memory to the learning and memory of aged humans (e.g., 
Bachevalier et al., 1991; Presty et al., 1987). Evidence continues to accrue that learning and 
memory acquisition (short-term memory) requires circuits through the hippocampus. Memory 
storage probably involves appropriate areas of association cortex (long-term store), and the 
retrieval and ability to manipulate data drawn from long-term storage (e.g., working memory) 
probably also requires intact circuits through the frontal lobe. Studies have more precisely 
identified the roles of the hippocampal and medial temporal lobe structures in the encoding 
and acquisition of new information and problems of memory with age. Recent findings 
indicate that stimulation of hippocampal neurons may result in proteins produced through the 
activation of immediate-early gene expression, which bind to specific synaptic 
phosphoproteins to consolidate the memory (Scanziani et al., 1996). In addition, transgenic 
models and mutant or conditional knockout mice with deletions, such as alpha-CAMKII and 
CREB (Silva et al., 1996; Kirkwood et al., 1997), may open windows to the underlying 
molecular mechanisms of age-related cognitive deficits, especially when linked to 
identification of such genes that manifest their effects late in life. These data could then be 
used in human population studies to determine the genetic linkages associated with 
behavioral and cognitive functions in the aging nervous system. 
Research now indicates that generalized neuron loss leading to cognitive loss is not an 
inevitable consequence of aging. While there is an association between loss of cognitive 
function and thinning of cortical layer 1 and demyelination (Peters et al., 1996), aged 
monkeys appear not to lose neurons uniformly in the neocortex and hippocampus. However, 
studies in rats show that neuron number is preserved in aged animals and that degeneration 
of these cells and reduction in receptor sites are not associated with behavioral impairments 
(Rapp and Gallagher, 1996). Problems in memory are often observed in older adults, but 
research on the neural basis for these behaviors needs animal models to further our 
understanding of how to deal with these age-associated deficits. Work has been progressing 
in using transgenic animals and molecular probes to elucidate molecular mechanisms 
underlying learning processes and retention of memory. Animal models thus provide a 
powerful means for analyzing the neuronal mechanisms of memory deficits that occur with 
aging. 
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