Normal aging and AIDS

Normal aging is accompanied by a wide range of changes in brain structure and function. In this work we seek to examine the hypothesis that normal aging results in neuropsychological findings similar to those produced by neuropsychological impairment related to AIDS. Specifically, we attempt to compare the level of neuropsychological performance in three groups: a normal elderly group (n = 46), a young group of AIDS patients (n = 36), and a young group of normal subjects (n = 22). The results indicated that, despite age differences between the normal elderly and AIDS patients, there was great similarity in the neuropsychological test performance of these two groups. In contrast, both groups demonstrated significantly different neuropsychological test performance than that evidenced by the younger normal controls. These results support the notion that neuropsychological changes related to normal aging are of a nature similar to those observed in AIDS and, therefore, affect functions subserved by frontal-subcortical brain regions.     

Hypotheses of aging in a long-lived vertebrate, Blanding's turtle (Emydoidea blandingii)

For 35 of the past 47 years, Blanding's turtles were studied on the University of Michigan's E.S. George Reserve in southeastern Michigan. Blanding's turtle is one of the longest-lived emydid turtles with individuals reaching ages greater than 75 years. We compared body sizes, reproductive traits and survival of Young, Middle, and Oldest age groups of Blanding's turtles to test predictions from two contrasting hypotheses of aging. The relative reproductive rate hypothesis predicts traits that increase the reproductive output or survival rates of older compared to younger individuals, whereas the senescence hypothesis predicts a reduction in reproductive output or survival in older versus younger individuals. Body size did not increase with age among groups; therefore, indeterminate growth was not a mechanism for increased reproductive output of the oldest individuals. Survivorship, reproductive frequency and size-adjusted mean clutch size were all higher in the Oldest age group compared to the younger age groups. Nest predation rate was highest in the Young age group compared to either group of older turtles. In nests that survived predation, the proportion of nests that failed entirely due to developmental problems was lowest in the Young, intermediate in the Middle, and highest in the Oldest age group. Successful nests produced similar numbers of hatchlings and similar sized hatchlings in all three age groups. Traits such as egg and offspring size, and offspring produced per nest did not support either the relative reproductive rate or the senescence hypothesis of aging. Increased embryo mortality in nests of older females compared to younger turtles supports predictions from the senescence hypothesis. Three traits; increased clutch size, reproductive frequency, and survivorship of individuals in the Oldest age group compared to younger turtles support the relative reproductive rate hypothesis for evolution of longevity.     

Regulation of Drosophila life-span: Effect of genetic background,sex, mating and social status

During the past decade, model organisms such as Drosophila have made it possible to identify individual genes and pathways that regulate organismal life-span. However, despite the progress made in Drosophila aging research, many longevity studies have often yielded controversial results that can be attributed to differences both in genetic background and in experimental design. Here, we describe the results of a systematic analysis of life-span comparisons in two laboratory wild-type strains. The main goal of these studies is to clarify the effects of social status, mating and sex on life-span with the aim of defining the optimal experimental design whereby the influence of these factors would be minimized. We find that differences in environmental factors and genetic background can be minimized by measuring the life-span of flies that are maintained as mixed-sex groups that allow for regular sexual and social contacts and seems to be more physiologically relevant for estimation of population’s life-span. Taken together, these results may be especially important for screens designed to search for genes that may be involved in longevity as well as for comparative analysis of strains in which the genetic background is unknown or in those cases where it is very difficult to equilibrate.     

Use of motor performance tests to differentiate aging effects from disease effects

The present study has demonstrated that behavioral testing can provide non-invasive methods for monitoring the time-courses of aging and disease processes. Performance on two of our tests changed linearly with increasing age in both cardiomyopathic and healthy hamsters, but these changes occurred at an earlier age in the CM hamsters than in healthy control hamsters. In addition, healthy hamsters showed age-related changes in performance on some tests, while sick CM hamsters did not show parallel changes. These results indicate that disease can modify the rate of change in some markers of aging, and thus they suggest that disease might be able to modify the aging process. However, such a preliminary hypothesis requires much further work. Performance on another behavioral test was shown to be stable throughout much of the lifespan of healthy hamsters, and yet disease in CM hamsters was clearly able to affect it. Thus it was possible to find some tests which discriminated between aging and disease effects, but only because the time-course of the disease we were studying was well defined. Most importantly, these results have suggested a way of thinking about the problem of disease in aging studies that may be more fruitful than others previously used. Examining the changes over time in both healthy subjects (putatively disease-free) and those with disease should allow one to determine which age-related changes are dependent on the presence of organic disease and to separate these from the changes which might inevitably occur solely from increasing age.     

Cell proliferation in the dentate gyrus of rat hippocampus is inhibited by soft diet feeding

BACKGROUND: Recently it has become well accepted that neurogenesis occurs in the dentate gyrus of the hippocampus, a region important to memory and learning function in rodents and humans. Reports show that neurogenesis in the hippocampus is regulated by certain factors, such as exposure to an enriched environment, physical activity, aging and stress. The relationship between the change in the task of chewing as one oral environmental factor, and the mechanisms of hippocampal neuron generation are unclear. OBJECTIVE: We examined whether cell proliferation varies by chewing tasks with different food textures in the dentate gyrus of the rat hippocampus. METHODS: Wistar rats were divided into two groups, one was fed a solid diet, known as the hard-diet feeding group, and the soft-diet feeding group, which was fed a powder diet containing the same components as the solid one for 3, 7, 16 and 24 weeks. Thymidine analog 5-bromo-2'-deoxyuridine (BrdU) was used as a marker of cell proliferation within the dentate gyrus of the hippocampus and olfactory bulb. RESULTS: The results of this study indicated that the total number of BrdU-positive cells in the hippocampal dentate gyrus significantly decreased with aging and were significantly fewer in the soft-diet feeding group than in hard-diet feeding group in 7-, 16- and 24-week-old rats after the BrdU injection. The change of BrdU-positive cell expression between soft and hard diets in 3- and 24-week-old rats was not observed in the olfactory bulb. CONCLUSION: It has been suggested that cell proliferation in the dentate gyrus of the rat hippocampus is characteristically suppressed by soft diet feeding.     

Anorectal functioning in fecal incontinence

Manometric testing was performed on three groups of subjects: 14 patients complaining of fecal incontinence, 14 age- and sex-matched continent patients, and 14 sex-matched younger normal controls. The younger group displayed significantly stronger contractions of the external anal sphincter and puborectalis than the two patient groups, which did not differ. No differences were found in the relaxation of the internal anal sphincter. The incontinent group required a significantly larger stimulus in order to detect rectal distension compared to either the continent patients or the younger normals. An additional group of unmatched normals and incontinent patients demonstrated significant differences in their ability to retain rectally infused saline. The patients leaked sooner and retained less;however, the performance of the normals was considerably reduced from that reported in previous studies. The aging process seems to result in weakening of the striated muscles of the anal canal, although fecal incontinence need not occur. The afferent limb of the anorectal sensorimotor mechanism does not necessarily deteriorate with aging. A lower threshold for sensation of rectal distension among continent individuals apparently helps them to avoid incontinent episodes, even though maximum contractile pressures in their anal canal are no different from a comparable group of incontinent individuals.     

Age-correlated changes in cerebral hemodynamics assessed by near-infrared spectroscopy

Cerebral hemodynamic responses due to normal aging may interfere with hormonal changes, drug therapy, diseases, life style, and other factors. Age-correlated alterations in cerebral vasculature and autoregulatory mechanisms are the subject of interest in many studies. Near-infrared spectroscopy (NIRS) is widely used for monitoring cerebral hemodynamics and oxygenation changes at the level of small vessels. We believe that the compensatory ability of cerebral arterioles under hypoxic conditions and the dilatatory ability of cerebral vessels due to vasomotion may decline with normal aging. To test this hypothesis we used frequency-domain NIRS to measure changes in cerebral tissue oxygenation and oxy- and deoxy-hemoglobin concentrations caused by hypoxia during breath holding. We also assessed cerebral vasomotion during profound relaxation. Thirty seven healthy volunteers, 12 females and 25 males, ranging from 22 to 56 years of age (mean age 35 +/- 11 years) participated in the study. We observed age-correlated changes in the cerebral hemodynamics of normal subjects: diminished cerebral hemodynamic response to hypoxia due to breath holding in middle-aged subjects (38-56 years) and reduced amplitude of cerebral hemodynamic changes due to vasomotion during rest. Snoring related changes in cerebral hemodynamics did not allow us to observe the effect of age in a group of snorers. The prolonged supine position influenced measured changes due to hypoxia. In this investigation NIRS methodology allowed detection of age-correlated changes in cerebral oxygenation and hemodynamics. Other variables, such as snoring or posture impacted the observations in our group of healthy volunteers.     

Regulation of adenosine formation by the heart

We think that the available data on adenosine formation suggest the two signals are responsible for adenosine release from cardiac myocytes: (1) the ratio of oxygen supply to demand and (2) agonist-triggered release of extracellular adenine nucleotides. We do not believe that the available data support the oxygen consumption hypothesis. The few studies which allow us to judge the relative importance of these two signals suggest that both hypoxia and sympathetic nerve stimulation release adenosine primarily by decreasing O2 supply:demand. Agonist triggered nucleotide release may be quantitatively important in situations in which decreased O2 supply/demand cannot explain increased release, i.e., isoproterenol and acetylcholine administration.     

Comparison study between electrogalvanic stimulation and local injection therapy in levator ani syndrome

Background and aims Two theories have been reported for the pathophysiology of levator ani syndrome: the spastic cycle hypothesis and the local inflammation (Tendinitis) hypothesis. This study compared two treatment modalities in order to determine which of the two hypotheses is more appropriate.Subjects and methods In this prospective study, Group EGS (n=22) underwent electrogalvanic stimulation twice a week. Group LI (n=31) underwent a local injection of a 40-mg triamcinolone acetonide mix with 1 ml 2% lidocaine into the maximal tender point of the arcus tendon in the levator ani muscle.Results The most common location of tenderness was the left anterior of the arcus tendon of the levator ani muscle. At the last follow-up (12 months), the LI group showed more relief, more improvement, and fewer failures than the EGS group. No difference was seen between the mean pain scores (verbal analog scale: 0–100) of the two groups at either the 1-week or the 12-month follow-up. However, the LI group showed better results at the 1-month, 3-month, and 6-month follow-ups.Conclusion The LI group showed better short-term results than the EGS group. Therefore, the tendinitis hypothesis seems to be the more reliable one for levator ani syndrome. However, because the subjective responses of the patients indicated that a sufficient level of patient satisfaction had not been achieved, we cannot positively conclude that the tendinitis hypothesis is the more reliable one for the pathophysiology of levator ani syndrome.     

The phase relationship between the circadian rhythms of locomotor activity and circulating melatonin in the pigeon (Columba livia)

The phase relationship between the circadian rhythms of locomotor activity and circulating melatonin levels under LD 12:12 and constant dim light conditions (LLdim) was examined in pigeons. Our new radioimmunoassay technique had sufficient sensitivity to detect the concentration of melatonin from a small quantity of plasma, which enabled us to measure locomotor activity simultaneously with circulating melatonin rhythms from each individual pigeon. The relationship of phase between the two circadian rhythms in LLdim was the same as in LD. The rhythms of locomotor activity and melatonin levels free-run but maintain the relation of 180 degrees out of phase in LLdim. These results do not contradict the hypothesis that melatonin may entrain the circadian rhythm of locomotor activity in the pigeon.     

Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study

DESIGN: The aim of this study was to determine the association between aging and adiponectin level from the aspect of the influence of renal function and sex hormones in humans. METHODS: Serum adiponectin and blood urea nitrogen (BUN) levels were measured in 964 subjects (372 males) aged 60.3+/-12.5 years. Testosterone and free testosterone levels were measured in 123 males, and estrone and estradiol levels were measured in 114 females. The subjects were divided into two age groups; 65 years of age or older (Age > or = 65 group) and less than 65 years of age (Age < 65 group). RESULTS: Adiponectin level increased linearly with aging in males, whereas it increased dramatically in females until their 50s. The patterns of changes in adiponectin were similar to those in BUN. In multiple- regression analysis using adiponectin as a dependent variable BUN was selected as a significant independent variable in all subjects and in subjects in the Age > or = 65 group, whereas bioactive sex hormones were not selected. CONCLUSIONS: A decrease in adiponectin clearance in the kidney may be the cause of high levels of adiponectin in the elderly. Adiponectin level seems to be influenced more strongly by BUN than by sex hormones and to be increased by a decline in renal function with aging.     

Smelling home can prevent dispersal of reef fish larvae

Many marine fish and invertebrates show a dual life history where settled adults produce dispersing larvae. The planktonic nature of the early larval stages suggests a passive dispersal model where ocean currents would quickly cause panmixis over large spatial scales and prevent isolation of populations, a prerequisite for speciation. However, high biodiversity and species abundance in coral reefs contradict this panmixis hypothesis. Although ocean currents are a major force in larval dispersal, recent studies show far greater retention than predicted by advection models. We investigated the role of animal behavior in retention and homing of coral reef fish larvae resulting in two important discoveries: (i) Settling larvae are capable of olfactory discrimination and prefer the odor of their home reef, thereby demonstrating to us that nearby reefs smell different. (ii) Whereas one species showed panmixis as predicted from our advection model, another species showed significant genetic population substructure suggestive of strong homing. Thus, the smell of reefs could allow larvae to choose currents that return them to reefs in general and natal reefs in particular. As a consequence, reef populations can develop genetic differences that might lead to reproductive isolation.     

Clinical findings of arteriosclerosis and serum lipoprotein(a) concentration in elderly patients

This study was conducted to evaluate the relationship between arteriosclerosis and lipoprotein(a) [Lp(a)] from the point of view of aging. A total of 354 patients (167 men) aged 60 or more were enrolled and serum Lp(a) levels, vascular risks, and complications were studied. Patients were divided into 3 groups according to age: group I (n = 73: aged 60 to 69), group II (n = 144: aged 70-79), and group III (n = 137: aged 80 or more). Vascular complications were assessed by carotid ultrasonography (US), ECG, and ankle pressure index (API), US findings were stratified according to the distribution of plaque lesions in unilateral and bilateral lesions, while plaque types were subdivided based on the morphology and US echogenicity. Male patients with risk factors (diabetes, hypercholesterolemia, cigarette smoking) as well as stroke were frequent in group I, indicating some selection bias. However, there was no difference in Lp(a) level among the three groups. Carotid lesions, especially bilateral lesions with more thickened plaques, and low API were both significantly frequent in group III. Logistic regression analysis showed that carotid lesions were influenced not only by aging, but also independently by high Lp(a) levels in group III, and by hypertension in group II. A high Lp(a) level was related to hypercholesterolemia and hypoechoic plaque. These findings indicated that atherosclerosis, which developed in both the carotid and peripheral arteries with aging, was related to different risks in each decade of life. Furthermore, it seems that a long period of high Lp(a) levels may promote the formation of hypoechoic plaque.     

Videofluorographic Assessment of Deglutitive Behaviors in a Rat Model of Aging and Parkinson Disease

Dysphagia is commonly associated with aging and Parkinson disease and can have a significant impact on a person’s quality of life. In some cases, dysphagia may be life-threatening. Animal models may be used to study underlying mechanisms of dysphagia, but paradigms that allow adequate imaging of the swallow in combination with measurement of physiological variables have not been forthcoming. To begin development of methods that allow this, we used videofluorography to record the deglutition behaviors of 22 Fisher 344/Brown Norway rats in young adult (9 months old), old (32 months old), and parkinsonian (unilateral lesion to the medial forebrain bundle) groups. We hypothesized that the old and parkinsonian rats would manifest deficits in deglutition behaviors analogous to those found in human clinical populations. Our results supported our hypothesis in that the old group demonstrated reductions in bolus transport speeds and mastication rate while the parkinsonian rats showed impairments in oral processing. Interpretation of these results should consider the particular animal model, lesion type, and videofluorographic protocol used in this work. Future studies will link swallow imaging data of this kind with physiological and anatomical data in a manner not possible with human participants.     

Age effects on preattentive and early attentive auditory processing of redundant stimuli: is sensory gating affected by physiological aging?

The frontal hypothesis of aging predicts an age-related decline in cognitive functions requiring inhibitory or attentional regulation. In Alzheimer's disease, preattentive gating out of redundant information is impaired. Our study aimed to examine changes associated with physiological aging in both pre- and early attentive inhibition of recurrent acoustic information. Using a passive double-click paradigm, we recorded mid-latency (P30-P50) and late-latency (N100 and P200) evoked potentials in healthy young (26 ± 5 years) and healthy elderly subjects (72 ± 5 years). Physiological aging did not affect auditory gating in amplitude measures. Both age groups exhibited clear inhibition in preattentive P50 and attention-modulated (N100) components, whereas P30 was not attenuated. Irrespective of age, the magnitude of inhibition differed significantly, being most pronounced for N100 gating. Inhibition of redundant information seems to be preserved with physiological aging. Early attentive N100 gating showed the maximum effect. Further studies are warranted to evaluate sensory gating as a suitable biomarker of underlying neurodegenerative disease.     

Use and application in clinical practice of the CASPAR criteria

Several classification criteria for psoriatic arthritis have been proposed in the literature but it is still unclear which one of them best represents the diseases' ample spectrum. None of these classification criteria have been universally accepted. New classification criteria (CASPAR) have been recently published. Their application is simple, fast and easy to perform. In addition, they show two important qualities. One is that they allow for the diagnosis of psoriatic arthritis even when there is no skin disease present at the moment of diagnosis. The other is is that it enables us to classify a patient as having psoriatic arthritis in spite of a positive rheumatoid factor. The CASPAR criteria have a sensitivity of 91.4% and a specificity of 98.7%. It seems, in contrast, that it is not as high for recent-onset psoriatic arthritis. Therefore establishing the definition of inflammatory arthritis becomes paramount.     

Adaptations of the aging animal to exercise: role of daily supplementation with melatonin

The pineal gland, through melatonin, seems to be of fundamental importance in determining the metabolic adaptations of adipose and muscle tissues to physical training. Evidence shows that pinealectomized animals fail to develop adaptive metabolic changes in response to aerobic exercise and therefore do not exhibit the same performance as control‐trained animals. The known prominent reduction in melatonin synthesis in aging animals led us to investigate the metabolic adaptations to physical training in aged animals with and without daily melatonin replacement. Male Wistar rats were assigned to four groups: sedentary control (SC), trained control (TC), sedentary treated with melatonin (SM), and trained treated with melatonin (TM). Melatonin supplementation lasted 16 wk, and the animals were subjected to exercise during the last 8 wk of the experiment. After euthanasia, samples of liver, muscle, and adipose tissues were collected for analysis. Trained animals treated with melatonin presented better results in the following parameters: glucose tolerance, physical capacity, citrate synthase activity, hepatic and muscular glycogen content, body weight, protein expression of phosphatidylinositol 3‐kinase (PI3K), mitogen‐activated protein kinase (MAPK), and protein kinase activated by adenosine monophosphate (AMPK) in the liver, as well as the protein expression of the glucose transporter type 4 (GLUT4) and AMPK in the muscle. In conclusion, these results demonstrate that melatonin supplementation in aging animals is of great importance for the required metabolic adaptations induced by aerobic exercise. Adequate levels of circulating melatonin are, therefore, necessary to improve energetic metabolism efficiency, reducing body weight and increasing insulin sensitivity.     

Utilidad y aplicación en la práctica clínica de los criterios CASPAR

Several classification criteria for psoriatic arthritis have been proposed in the literature but it is still unclear which one of them best represents the diseases’ ample spectrum. None of these classification criteria have been universally accepted. New classification criteria (CASPAR) have been recently published. Their application is simple, fast and easy to perform. In addition, they show two important qualities. One is that they allow for the diagnosis of psoriatic arthritis even when there is no skin disease present at the moment of diagnosis. The other is is that it enables us to classify a patient as having psoriatic arthritis in spite of a positive rheumatoid factor. The CASPAR criteria have a sensitivity of 91.4% and a specificity of 98.7%. It seems, in contrast, that it is not as high for recent-onset psoriatic arthritis. Therefore establishing the definition of inflammatory arthritis becomes paramount.     

Evaluation of the health inpact of the floods in the Gard on respiratory health of disaster victims

In 2002 the Gard was subjected to exceptional flooding, as much by their size as by the number of affected community victims, more than the Nimes floods in October 1988. No community was spared and more than 800 families had to be rapidly re-located. As the medical bibliography of the impact of the floods on respiratory heath was not conclusive we have proposed to the CHU of Nimes a hospital clinical research project undertaken by the members of RNSA, the Institute of Public Health of Brussels and the European Centre for Medical Bioclimate Research and Teaching, who have accepted to share their knowledge with the Gard. It seems to us to be indispensable, considering the certifications made by the professionals on the health on the department, to validate the study methods for the evaluation of the health impact of the floods, with regard to the development of moulds in the environment, so as to recognise the risk to health, in the very special circumstances, and so allow the mobilisabion of useful resources more rapidly than previously. The new floods to which the department was subjected in December 2003 made us regret that we had not developed this project more quickly.