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The age-related decline in lymphocyte development and function coincides with impaired zinc status in the elderly. Thymic involution and reduced immune responsiveness are classic hallmarks of both aging and zinc deficiency, resulting in decreased host defense and an increased susceptibility to infections. Thus, compromised zinc status associated with aging may be an important contributing factor in reduced thymopoiesis and impaired immune functions. Our goal in this study was to understand how dietary zinc supplementation affects thymopoiesis in aged mice. We hypothesized that impaired zinc status associated with aging would mediate the decline in thymic function and output and that restoring plasma zinc concentrations via zinc supplementation would improve thymopoiesis and thymic functions. In this study, groups of young (8 wk) and aged (22 mo) mice were fed a zinc-adequate (30 mg/kg zinc) or zinc-supplemented diet (300 mg/kg) for 25 d. Aged mice had impaired zinc status, with zinc supplementation restoring plasma zinc to a concentration not different from those of young male C57BI/6 mice. Zinc supplementation in aged mice improved thymopoiesis, as assessed by increased total thymocyte numbers. In addition, improved thymic output was mediated in part by reducing the age-related accumulation of immature [CD4.sup.-][CD8.sup.-][CD44.sup.+][CD25.sup.-] thymocytes, as well as by decreasing the expression of stem cell factor, a thymosuppressive cytokine. Taken together, our results showed that in mice, zinc supplementation can reverse some age-related thymic defects and may be of considerable benefit in improving immune function and overall health in elderly populations.

The purpose of this study was to determine whether glycine is effective in correcting the age-related change in the N-methyl-D-aspartate (NMDA) receptor complex. Autoradiographic analysis of [[sup.3]H]MK801 and NMDA-displaceable [[sup.3]H]glutamate binding was performed with 0, 10, 30 and 100 [Mu]M glycine on brain tissue from 3-, 10-, and 24-30-month-old C57B1 mice. Glycine, even at 10 [Mu]M, enhanced binding to both the NMDA and MK801 binding sites in all age groups. Glycine was notable to reduce the absolute difference in [[sup.3]H]glutamate binding to NMDA sites between 3-and 24-month-olds. Low micromolar concentrations of glycine exacerbated the aging difference in [[sup.3]H]MK801 binding between young and old mice, but 100 [Mu]M glycine produced smaller aging differences that were similar to those seen with no glycine. This study suggests that glycine may enhance NMDA receptor function in old animals, but it does not appear to correct the underlying problem with the NMDA receptor in aged animals.

Abstract Background C57BL/6 mice show a relationship during aging between NMDA receptor expression and spatial reference memory performance in a 12-day task. The present study was designed to determine if age-related deficits could be detected with a shorter testing protocol and whether these deficits showed a relationship with NMDA receptors. Mice were trained in a reference memory task for two days in a Morris water maze. Cued testing was performed either after or prior to reference memory testing. Crude synaptosomes were prepared from prefrontal/frontal cortex and hippocampus of the mice that underwent reference memory testing first. NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting. Results Young mice showed significant improvement in probe and place learning when reference memory testing was done prior to cued testing. A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing. There was a significant decline in the protein expression of the ε2 and ζ1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex. The subunit changes showed a significant correlation with both place and probe trial performance. Conclusion The presence of an age-related decline in performance of the reference memory task regardless of when the cued trials were performed suggests that the deficits were due to factors that were unique to the spatial reference memory task. These results also suggest that declines in specific NMDA receptor subunits in the synaptic pool of prefrontal/frontal brain regions contributed to these age-related problems with performing a spatial reference memory task.

The current study applied a rodent-based Morris water maze (MWM) protocol to an investigation of search performance differences between young and older adult humans. To investigate whether similar age-related decline in search performance could be seen in humans based on the rodent-based protocol, we implemented a virtual MWM (vMWM) that has characteristics similar to those of the MWM used in previous studies of spatial learning in mice. Through the use of a proximity to platform measure, robust differences were found between healthy young and older adults in search performance. After dividing older adults into good and poor performers based on a median split of their corrected cumulative proximity values, the age effects in place learning were found to be largely related to search performance differences between the young and poor-performing older adults. When compared with the young, poor-performing older adults exhibited significantly higher proximity values in 83% of 24 place trials and overall in the probe trials that assessed spatial learning in the absence of the hidden platform. In contrast, good-performing older adults exhibited patterns of search performance that were comparable with that of the younger adults in most place and probe trials. Taken together, our findings suggest that the low search accuracy in poor-performing older adults stemmed from potential differences in strategy selection, differences in assumptions or expectations of task demands, as well as possible underlying functional and/or structural changes in the brain regions involved in vMWM search performance. [ABSTRACT FROM AUTHOR]

This study investigated whether the aging process in dogs is associated with an increased sensitivity to inhalation anesthesia and whether age-related changes in glutamate receptors are related to the increased sensitivity. The mean minimum alveolar concentration (MAC) of isoflurane was 1.82 [+ or -] .08% for 2-3 year olds and 1.45 [+ or -] .06% for 11 years olds, indicating that there was an increased potency of isoflurane in the older dogs as compared to the young. These older animals also showed a significant decrease in binding of [[sup.3]H]glutamate and [[sup.3]H]dizocilpine ([[sup.3]H]MK801) to N-methyl-D-aspartate (NMDA) receptors in multiple cortical and hippocampal regions. The density of binding to NMDA receptors in the cortex, using a single concentration of ligand, correlated significantly with individual MAC values. These results demonstrate that dogs experience an increase in anesthetic potency with increased age, similar to humans, and that age-related changes in the NMDA receptor may represent one mechanism underlying this increased sensitivity to anesthesia.

Glutamate is a major neurotransmitter in the mammalian central nervous system. In a key event during nerve impulse transmission glutamate is released from vesicles in the presynaptic neuron, and travels [...]