[H]Paroxetine binding in human platelets in relation to age and sex

The binding of [³H]paroxetine to serotonin uptake sites in human platelets from 47 individuals between 15 and 95 years of age was investigated. There were no significant age-related changes in maximal binding capacity (B_max) or apparent binding affinity (K_d). There were no significant differences in binding between males (n = 19) and females (n = 28).     

Circadian and age-related modulation of thermoreception and temperature regulation: mechanisms and functional implications

At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including thermoreception, thermogenesis and conservation, heat loss, and central regulation. Whereas some changes are related to the aging process per se, others appear to be secondary to other factors, for which the risk increases with aging, notably a decreased level of fitness and physical activity. Moreover, functional implications of the body temperature rhythm are discussed. For example, the relation between circadian rhythm and thermoregulation has hardly been investigated, while evidence showed that sleep quality is dependent on both aspects. It is proposed that the circadian rhythm in temperature in homeotherms should not be regarded as a leftover of ectothermy in early evolution, but appears to be of functional significance for physiology from the level of molecules to cognition. A new view on the functional significance of the circadian rhythm in peripheral vasodilation and the consequent out-of-phase rhythms in skin and core temperature is presented. It is unlikely that the strong, daily occurring, peripheral vasodilation primarily represents heat loss in response to a lowering of set point, since behavioral measures are simultaneously taken in order to prevent heat loss. Several indications rather point towards a supportive role in immunological host defense mechanisms. Given the functional significance of the temperature rhythm, research should focus on the feasibility and effectiveness of methods that can in principle be applied in order to enhance the weakened circadian temperature rhythm in the elderly.     

The relationship of age and cardiovascular fitness to cognitive and motor processes

Older and younger aerobically trained and sedentary adults participated in an S1-S2-S3 paradigm designed to elicit event-related potential (ERP) and behavioral responses to determine the influence of cardiovascular fitness on cognitive and motor processes. The paradigm provided warning (S1) as to the difficulty level of an upcoming decision task (S2). Participants had to decide the taller of two bars on presentation of S2 but hold their response until S3, to which they indicated their choice motorically. Results revealed age-related differences for ERP measures as older participants showed increased amplitude of the stimulus preceding negativity (SPN) prior to S2, and longer latencies and equipotentiality of P3 in response to S2. Fitness effects were also observed for the contingent negative variation (CNV) with decreased amplitude for fit relative to sedentary individuals. Age interacted with fitness for P3 latency to S2 as older sedentary individuals showed the longest latency followed by older fit and both younger groups. No significant group differences were observed for reaction time (RT) to S3. Therefore, physical fitness is associated with attenuation of cognitive decline in older individuals and greater economy of motor preparation for both young and older participants.     

Effects of L-carnitine on neutrophil functions in aged rats

Several age-related alterations occur at the cellular level in the immune system leading to a decrease in the immune response. The present study was designed to determine the effect of L-carnitine on impaired neutrophil functions of aged rats. For this reason, superoxide anion radical production, chemotaxis and phagocytic activity were studied in the neutrophils obtained from the peripheral blood of young and old rats. We orally gavaged L-carnitine (50 mg/kg b.w. per day) or control vehicle into young (2 months) and aged (24 months) rats for 30 consecutive days. The neutrophils of aged rats exhibited an increase in superoxide anion production and decline in phagocytosis and chemotaxis when compared with that in young rat neutrophils. Superoxide anion production in aged rats was significantly decreased by L-carnitine treatment which was accompanied with a significant enhancement of chemotactic and phagocytic activity being restored to control levels. These findings demonstrated that L-carnitine is capable of restoring the age-related changes of neutrophil functions.     

Age-related changes in the articular cartilage of human sacroiliac joint

 Iliac and sacral articular cartilage of 25 human sacroiliac joints (1–93 years) are examined by light microscopy and immunohistochemistry in order to gain further insight into the nature and progress of degenerative changes appearing during aging. These changes can already be seen in younger adults as compared to cartilage degeneration known in other diarthrodial joints. Structural differences between sacral and iliac cartilage can already be observed in the infant: the sacral auricular facet is covered with a hyaline articular cartilage, reaching 4 mm in thickness in the adult and staining intensely blue with alcian blue at pH1. Iliac cartilage of the newborn is composed of a dense fibrillar network of thick collagen bundles, crossing each other at approximately right angles. A faint staining with alcian blue suggests a low content of acidic glycosaminoglycans. In the adult, iliac cartilage becomes hyaline and its maximal thickness reaches 1–2 mm. Both articular facets exhibit morphological changes during aging that are more pronounced in the iliac cartilage and resemble osteoarthritic degeneration; the staining pattern of the extracellular matrix becomes inhomogenous, chondrocytes are arranged in clusters and the articular surface develops superficial irregularities and fissures. Sometimes fibrous tissue fills up these defects. Nevertheless, large areas of iliac cartilage remain hyaline in nature. Sacral articular cartilage often remains largely unaltered until old age. The sacral subchondral bone plate is usually thin and shows spongiosa trabeculae inserted at right angles, suggesting a perpendicular load on the articular facet. Iliac subchondral spongiosa shows no definite alignment and joins the thickened subchondral bone plate in an oblique direction. The iliac cartilage therefore seems to be stressed predominantly by shearing forces, arising from the changing monopodal support of the pelvis during locomotion. The subchondral bone plate on both the iliac and sacral auricular facet is penetrated by blood vessels that come into close contact with the overlying articular cartilage. These vessels may contribute to the high incidence of rheumatoid and inflammatory diseases in the human sacroiliac joint. Immunolabelling with an antibody against type II collagen reveals a diminished immunoreactivity in the upper half of adult sacral cartilage and only a faint and irregular labelling in the iliac cartilage. Type I collagen can be detected in a superficial layer on the sacral articular surface and around chondrocyte clusters in iliac cartilage, as in dedifferentiating chondrocytes during the development of osteoarthritis. Accepted: 22 April 1998     

Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice

A loss of hippocampal neurons and synapses had been considered a hallmark of normal aging and, furthermore, to be a substrate of age-related learning and memory deficits. Recent stereological studies in humans have shown that only a relatively minor neuron loss occurs with aging and that this loss is restricted to specific brain regions, including hippocampal subregions. Here, we investigate these age-related changes in C57BL/6J mice, one of the most commonly used laboratory mouse strains. Twenty-five mice (groups at 2, 14, and 28–31 months of age) were assessed for Morris water-maze performance, and modern stereological techniques were used to estimate total neuron and synaptophysin-positive bouton number in hippocampal subregions at the light microscopic level. Results revealed that performance in the water maze was largely maintained with aging. No age-related decline was observed in number of dentate gyrus granule cells or CA1 pyramidal cells. In addition, no age-related change in number of synaptophysin-positive boutons was observed in the molecular layer of the dentate gyrus or CA1 region of hippocampus. We observed a significant correlation between dentate gyrus synaptophysin-positive bouton number and water-maze performance. These results demonstrate that C57BL/6J mice do not exhibit major age-related deficits in spatial learning or hippocampal structure, providing a baseline for further study of mouse brain aging.     

In vivo vibrational wave propagation in human tibiae at different ages

Summary Vibrational wave propagation was tested in vivo on the tibial bone of both legs of 56 female volunteers. The impact was produced by a hammer with a force strain gauge and the response was monitored by two accelerometers. The peak amplitude of the accelerations, the velocity of the acceleration wave propagation and damping were analysed for comparison among the different age groups. The results showed significant negative correlations between age and the peak amplitude of acceleration, and the velocity of acceleration wave propagation (p<0.01). The damping time of the acceleration wave also had a negative correlation with age. These findings suggested that age differences were related to the differences in the mechanical properties of bone. With reduction of bone mineral density, the velocity of the vibrational wave propagation would decrease, with simultaneous increase in impedance. In addition, wave absorption would be accelerated. It is suggested that this method could be used as an indicator of bone density. The method could also be developed to provide an index to monitor the progress of osteoporosis. Visiting research assistant from the Department of Sport Medicine, Chengdu College of Physical Education, Chengdu, People's Republic of China Visiting research assistant from Seoul National University, Seoul, South Korea     

Age and neurochemical correlates of radial maze performance in rats

Young adult (8 months) and aged (26 months) female Wister rats were tested in a 12-arm radial maze in which the optimal strategy was to enter all arms without a repetition. In order to determine if possible age-associated alterations in behavior were correlated with defects in cholinergic. GABAergic and adrenergic neurons in the hippocampus and cerebral cortex, the activities of choline acetyltransferase (CAT), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) were assayed in these regions of all animals after testing in the radial maze. In the maze, the aged rats continued to perform at the chance level after 15 trials, whereas the young rats had virtually mastered the task. The only significant neurochemical age effect was an increase in hippocampal TH. However, analysis of individual differences among rats revealed positive correlations between maze performance and hippocampal CAT in the aged group and cortical GAD in both the young and aged groups.     

Age-related progression of tau pathology in brains of baboons

Recently, cytoskeletal changes associated with abnormally phosphorylated tau protein were demonstrated in neurons and glial cells of two aged baboons (Papio). The present study examines the effects of age on the development of tau pathology in baboons. Brains of 50 baboons ranging in age from 1 to 30 years were categorized into four age groups: Group I: 1–10 years [n = 9], group II: 11–20 years [n = 13], group III: 21–25 years [n = 17], group IV: 26–30 years [n = 11]). Whole hemisphere sections (100 μm) were examined using phosphorylation-dependent anti-tau antibodies. Cytoskeletal changes were completely absent in animals of group I. In group II four animals (31%) exhibited cytoskeletal changes which were rated as mild or moderate. In group III abnormal tau was found in 12 brains (71%) ranging in severity from mild to severe. Finally, in group IV 10 out of 11 animals (91%) exhibited some degree of tau pathology which was rated as severe in 4 animals (36%). A statistically significant relationship was found between advancing age and progression of tau pathology in baboons. In conclusion, the present findings underline the value of the baboon as a potential nonhuman primate model for age-related tau pathology afflicting the human brain.