Reduced Febrile Responses to Peripheral and Central Administration of Pyrogen in Aged Squirrel Monkeys

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10–14 years of age compared with that of younger animals. In response to injections of endotoxin into the lateral cerebral ventricle (ICV), animals over 10 years old showed small or no fevers. Injections of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen and prostaglandin, augmented fever caused by IV and ICV endotoxin and hyperthermia caused by ICV PGE₂ in animals under 10 years of age. However, in older animals probenecid increased fever caused by ICV endotoxin only, although the increased response was still less than one quarter that of younger animals. The results indicate that old squirrel monkeys have decreased febrile responses that may be traced to alterations in central sensitivity to pyrogens.     

Behavioral and neurochemical effects of dietary tyrosine in young and aged mice following cold-swim stress

The effects of dietary supplements of L-tyrosine on aggressive behavior, locomotor activity, and brain neurochemical changes were assessed in young and aged mice following cold-swim stress. Male CF-1 mice, ages 3 months and 21 months, were maintained on a semi-synthetic basal diet for one week, pretested for aggressive behavior and locomotor activity, then switched to diets modified by the addition of tyrosine or casein (control). After one week on the diet supplements, half of the mice were stressed by cold water swim and all were again subjected to behavioral testing. Members of each group were sacrificed for analysis of amino acids and monoamines in brain tissue and corticosterones in blood. It was found that tyrosine supplementation induced a marked increase in aggressive behavior in young, nonstressed mice but not in aged mice. Stress decreased the aggressiveness of both young and aged mice, and tyrosine prevented this stress-induced decrease in both groups. Young mice exhibited no changes in locomotion as a function of stress or diet. However, tyrosine prevented decreases in locomotion observed on second testing of both stressed and nonstressed older mice. The effect of stress was to lower levels of brain norepinephrine (NE) and dopamine (DA) in both young and aged mice. Tyrosine supplementation increased brain tyrosine and DA in both groups. Brain serotonin levels were lower in the aged mice compared to the younger ones, and this was associated with relatively higher concentrations of 5-hydroxyindoleacetic acid. It appears that tyrosine supplementation was effective in reducing the effects of stress in the aged animals, possibly by virtue of its relationship to catecholamine metabolism.     

Age-related changes in proton T1 values of normal human brain

To determine whether there were age-related changes In the brain tissue of 55 healthy adult volunteers (29 men, 26 women; 18-72 years old) without known brain abnormalities, a standard inversion-recovery technique was optimized for precise and accurate T1 measurement within the constraints of a 15-minute examination. Measurements of water proton T1 were obtained in eight brain regions. T1 increased with age in the genu (P < 0.001) (analysis of variance), frontal white matter (P < 0.05), occipital white matter (P < 0.05), putamen (P < 0.001), and thalamus (P << 0.001). A significant decrease in T1 with age was found in cortical gray matter (P < 0.05). Thus, age-related changes in T1 are present in a healthy population, even if extremes of age are excluded, suggesting that T1 values generally increase with age. However, increases in T1 were also observed in the genu, putamen, and thalamus of a substantial fraction of volunteers less than 35 years old. Aging healthy persons can show subtle, nonsymp- tomatic brain changes, suggesting that brain aging is associated with occult processes that can begin at a relatively early age.     

老年黄斑变性研究

通过对老年黄斑变性(AMD)的流行病学、发病因素和视功能等综合研究,显示此病已成为对老年人值得注意的致盲眼病。虽然多数患者为AMD干性和尚有较好视力,但各种视功能测定显示可有不同程度损害。控制光损害和改善微量元素代谢有助于AMD的早期预防和治疗,此病也成为亚洲国家防盲的一项重要任务。     

Interregional correlations of resting cerebral glucose metabolism in old and young women

A correlational analysis of normalized (regional to whole-brain) regional cerebral metabolic rates for glucose obtained in the 'resting' state (eyes covered, ears plugged) using [18F]fluorodeoxyglucose, demonstrated differences between old and young women in patterns of functional associations. Fifteen healthy young (age less than 40 years) and 17 healthy old women (age greater than 64 years) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest. The old women had fewer and less positive correlations between pairs of metabolic ratios in the frontal and parietal cortices. The results suggest an age-related reduction in frontal and parietal functional interactions in the 'resting' state that is consistent with a prior correlation analysis using a low resolution ECAT II scanner on young and old men. Reduced functional interactions may reflect age-related cognitive changes.     

Caffeine attenuates scopolamine-induced memory impairment in humans

Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.     

Caloric restriction enhances evoked DA overflow in striatum and nucleus accumbens of aged Fischer 344 rats

Previous studies have shown deficits in DA neuronal systems in senescence. Other studies indicate that prolonged dietary restriction can attenuate many of the detrimental effects of age. We have shown previously using in vivo electrochemistry that K⁺-evoked striatal DA overflow decreases as a function of age. This was a regional effect that appeared to be due to functional changes in DA neurons, rather than a decrease in the storage and synthesis of DA. In the present studies, we used in vivo electrochemistry to investigate the effects of caloric restriction on age related decreases in K⁺-evoked DA overflow along a dorsal to ventral axis in the striatum of aged female Fischer 344 rats. Aged (26–28-month-old) diet restricted animals (DRF) showed evoked DA overflow that was significantly greater in amplitude and duration compared to aged (26–28-month-old) ad lib fed animals (ALF). These results provide additional evidence that decreased DA neuronal function resulting from age is improved by caloric restriction.     

Age-related changes in the morphology of preganglionic neurons projecting to the paracervical ganglion of nulliparous and multiparous rats

The aim of this study was to investigate age-related changes in preganglionic neurons in the lumbar and sacral spinal cord of the female rat that may underlie impaired control of the urogenital system in old age. Preganglionic sympathetic and parasympathetic neurons of young adult, aged nulliparous and aged multiparous rats were identified by retrograde tracing with cholera toxin subunit-B and subsequent immunocytochemistry. Labeled preganglionic neurons were scanned, processed and analyzed using the confocal microscope. Measurements were made of soma area, number of primary dendrites, number of dendritic branch points and total dendritic length. There were significant decreases in the number of primary dendrites, number of dendritic branch points and total dendritic length of sympathetic preganglionic neurons in both nulliparous and multiparous aged rats compared to the young adult group. No significant differences were found in the dendritic morphology of aged parasympathetic preganglionic neurons. Soma area was not significantly different between age groups for sympathetic or parasympathetic preganglionic neurons. These changes in dendritic morphology may result in altered control of the lower urogenital tract in aged nulliparous and multiparous female rats.     

Delay-dependent short-term memory deficits in aged rats

Separate groups of rats of three ages (6 month, 15 month or 24 month) were trained in a two-lever operant chamber on one of two versions of a paired-trial delayed response task involving either matching or non-matching of the choice response to a sample lever. The older rats were unimpaired in learning either version of the task during initial training with no (0 s) delay between the sample and choice responses. However, when variable 0–24 s delay intervals were introduced, the 24-month group was impaired on acquisition of the delayed non-matching task, and both the 15- and 24-month groups were impaired on acquisition of the delayed matching task compared to the 6-month group. Deficits in the older groups in asymptotic performance were attributable to an impairment at longer delay intervals whilst maintaining near perfect performance at the shorter delay intervals, suggesting a selective short-term memory impairment. The delay-dependent deficits of the older groups were not ameliorated by the muscarinic agonist arecoline or the cholinesterase inhibitor physostig-mine, and so failed to corroborate a cholinergic interpretation of the observed age-related impairment in short-term memory.