Some aspects on the relationship between lipids, neurotransmitters, and aging.

A relationship is discussed between free radicals, lipid metabolism, neurotransmitters, and aging. Almost all of the lipid fractions of nerve tissue are heavily exposed during aging to the deleterious effects of a continuous formation of free radicals. In comparative terms, brain tissue has less enzymatic capacity to lower or counteract the rate of lipid peroxidation. However, various defense mechanisms exist that enable phospholipid reconstitution to occur and their metabolic activity to be maintained through reutilization of products arising from their biosynthesis and turnover. The effect of hyperoxygenation or hypoxygenation in association with free radicals generation on neurone stability and neurotransmitters reveals different susceptibilities to neuronal stimuli- and release quotients related to aging. With respect to the relationship between the environment and aging, neurotransmitter mechanisms, exemplified by that of dopamine and its turnover, play an important role in coping with stress, iatrogenic and toxic factors during aging. Possible pharmacological and other ways of mitigating age-related changes by means of protective reactions, accelerated repair processes, and compensatory mechanisms are discussed.

Changes in thyroid hormones and serum lipids of aged women following thyroidectomy.

Thyrotropin (TSH), thyroxine (T24) 3,5,3403 triiodothyronine (T23), serum lipid levels and ECG findings in females who underwent thyroidectomy 2-44 years earlier, were compared to those of similar controls with intact thyroid. Pathological ECG is more frequent in thyroidectomized persons who also exhibit higher thyrotropin and lower HDL-cholesterol levels. The results indicate that thyroidectomized state should be regarded and controlled as a possible condition of subclinical hypothyreosis, being a risk factor of cardiovascular diseases.

Relationship between a long-term treatment of 2-mercaptoethanol and protein metabolism in the ageing rat.

Female RLEF1/Lati rats were chronically treated with 2-mercaptoethanol in a dose of 13 micrograms.100 g bw-1.day-1 dissolved in drinking water. During a 48-h experiment 15N-labelled glycine was given orally in a dose of 5 mg 15N.kg bw-1 and urine samples were collected and analysed by an emission spectrometric isotope method. Protein synthesis and nitrogen excretion rate constants were calculated according to the three-pool model, and 3-methylhistidine excretion rates were also determined. 2-Mercaptoethanol appears to influence protein metabolism; however, the slower rates of protein synthesis proved to be apparent in almost all groups of treated rats. Protein synthesis and nitrogen excretion rate constants have exceptionally high values in 2-year-old rats, possibly explained by the occurrence of hypercompensation mechanisms in old age. These were reflected by the excretion rates of 3-methylhistidine which were reduced as a result of sulphhydryl group interactions in age-dependent cellular metabolic changes.

Effect of smoking on different biological parameters in aging mice.

To investigate the harmful effect of smoking three groups of CBA/Ca male mice of different ages were subjected to smoking for different time durations. Body weight changes and acute cold tolerance were measured throughout the experiment. Thyroid hormone levels (T4, T3), TSH and lipid peroxidation products (as malondialdehyde and lipofuscin) were determined from either the blood or some organs. There was a decrease in body weight related to aging and it was most pronounced in the oldest animals (Group III). However, significant body-weight loss due to smoking was found in the youngest animals (Group I). Similarly, smoking resulted in a body-weight loss of the other two older groups (Groups II and III) as well. The greatest change in withstanding cold stress was measured in Group I and less so in Group II, as a consequence of smoking. Simultaneously, the youngest animals (Group I) showed the most remarkable changes in thyroxine (T4) and 3,3,4-triiodothyronine (T3) serum concentrations. Both hormone levels were significantly lower in the smokers. The T3 serum levels of the oldest animals (Group III) did not differ, while the T4 levels apparently increased. The TSH blood level in the oldest group was lower (by 20%) in the smokers compared to controls. Malondialdehyde (MDA) and lipofuscin content in most of the organs were considerably higher in the aging animals than those of the younger ones. The most significant elevations of these lipid peroxidation products were found in the smokers compared to the age-matched controls. The present results indicate that smoking probably accelerates the aging process.

Effect of aging on cold tolerance and thyroid activity in CBA/Ca inbred mice.

Relationships between cold tolerance, serum levels of thyroxine (T4), thyronine (T3), and thyrotropine (TSH), and thyroid morphometry have been investigated in male CBA/Ca inbred mice at various ages through their life span. From the data obtained it appeared that there was an age-related decrease in cold tolerance up to 18 months of age which was followed by an increase, the age effect being most apparent in relation to cold resistance and cold tolerance during the recovery period following cold exposure. The age-related changes in cold tolerance appeared to be associated with changes in the serum concentrations of T3, T4, and TSH. In contrast to the T3 serum levels which showed a decrease at 36 months, the thyroxine contents showed a perceptible decrease from the age of 12-18 months onwards. A similar pattern was observed for the TSH levels, with a peak at 21 months, followed by a decline at 30 months. A relationship with age between serum T4 level and thyroid weight was indicated together with structural changes in the thyroid gland, particularly during senescence, for example the size and number of thyroid epithelial cells had become enlarged by 30 months of age.

Effect of cigarette smoke and 2-mercaptoethanol administration on age-related alterations and immunological parameters.

In old CBA/Ca mice the effect of cigarette smoke was compared with that of 2-mercaptoethanol (2-ME) treatment. It could be stated that spontaneous death was more frequent in animals kept in cigarette smoke than in the control animals. Prevalence of hepatocellular carcinoma was higher in animals kept in cigarette smoke than in the controls. After 2-ME treatment the occurrence of hepatocellular carcinoma was significantly lower and animals without disorders were more frequent than in smokers. Body weights were lower in animals kept in cigarette smoke and differences in organ indices could be observed, too. Immunological changes were also demonstrated: in mice kept in cigarette smoke the reactivity against a foreign antigen such as sheep erythrocytes (SRBC) was lower, while after 2-ME treatment it was higher than in their controls using direct plaque formation technique. The ratio of normal reactivity (against SRBC) and autoreactivity (against mouse erythrocytes) showed a decrease in smoker animals, and an increase in the 2-ME-treated ones. The experiments showed a deleterious effect of cigarette smoke and a beneficial effect of 2-ME on age-related alterations.

Effect of 2-mercapto-ethanol on some brain biochemical characteristics and behavioural changes in the ageing CBA/Ca mice.

Male CBA/Ca inbred mice were treated with a dose of 8 micrograms 2-mercapto-ethanol per animal per day in the drinking water from the age of 5 months onwards up to the age of 24 months. Dopamine release was greatly decreased in old animals in contrast to the elevation of dopamine release in the treated mice. Similarly, an elevated malondialdehyde content in brain homogenates was also observed in the aged treated animals compared with their controls. No essential differences were observed in locomotor activity and learning between treated an control mice.

Effect of an antioxidant compound (2-mercaptoethanol) on the nerve terminals of the aging small intestine.

The effect of 2-mercaptoethanol (2-ME) treatment on the nerve elements of the small intestine has been investigated in old mice. In control animals only a few synapses and a very small number of vesicles were found in the nerve terminals. Some of the nerve fibers were observed to be degenerating. After drinking 2-ME daily for 17 months, both the number of synapses and vesicles within the nerve terminals increased. No degenerated fibers were observed. It is assumed that 2-ME has a beneficial influence on the peripheral intestinal nervous system increasing the number of synapses and the vesicle population in the nerve terminals.

Effect of 2-mercaptoethanol on posthypoxic and age-related biochemical and behavioural changes in mice and rats.

2-Mercaptoethanol (2-ME) has a beneficial effect on the mean life span of laboratory rodents. This paper deals with the effects of 2-ME on changes of dopamine release from brain slices of old aged or hypoxia exposed mice and rats. The results were compared with data which reflect spontaneous peroxidation of brain lipid constituents. In addition, adequate behavioural properties were studied. Long-term 2-ME treatment for months abolishes the age-related decrease of transmitter release and prevents changes in malondialdehyde formation. If age-dependent release failure is already established, then neither single high doses of 2-ME nor repeated treatment for 3 weeks are effective. Posthypoxic release inhibition is prevented by a 2-ME pretreatment for 3 weeks but not by an acute single application even at high dosages. The preventive effect of 2-ME is a mediated one rather than an immediate direct action. Age-related behavioural deficits, such as locomotor activity, habituation performance and learning ability, do not reflect any effect of 2-ME long-term treatment.

Changes of organ indices of CBA/Ca inbred mice as function of age.

Weight changes of seven organs: brain, heart, lungs, liver, spleen, small intestine, and kidneys, were analyzed during aging of male CBA/Ca inbred mice. Data were collected as absolute organ weights, organ weights related to body, as well as brain weights. It was established that most organs increase their weight up to nearly two years of age, after which there is a dramatic decline. Body weight shows a distinct plateau or constancy along the lifespan of the animals; consequently, body weight seems to be generally the most favorable reference point to express some of the physiological changes and parameters of the aging organism. Variation coefficients of the organ weights generally become higher with age.

Effect of 2-mercaptoethanol on some metabolic indices of ageing of CBA/Ca inbred mice.

It has been shown in several studies that 2-mercaptoethanol (2-ME) improves the life span and aspects of life performance of laboratory animals. To obtain further details on the beneficial effects of 2-ME, a long-term study has been performed on male CBA/Ca inbred mice treated with this antioxidant. Four month-old mice were each given 4 micrograms of 2-ME in physiological saline via intraperitoneal (i.p.) injection 3 x per week. Measurements were made of the following: cold tolerance (heat performance), apparent total body protein turnover (T1/2), changes in the major lipid and fatty acid compositions of the liver, superoxide dismutase activity and formation of malondialdehyde and observations on a range of pathological changes. It was found that the basal rectal temperatures of the treated mice were higher and in the oldest group, heat performance capacity was better than those of the controls. After about 1 year of age the apparent biological half-life time of total body protein (T1/2) was observed to be shorter in the treated mice. Significant increases were observed to occur in the proportions of the polyunsaturated fatty acids in the lipids of the liver in the mice injected with 2-ME. Although no differences were observed in the superoxide dismutase activities, malondialdehyde concentrations in the livers of the experimental mice were significantly increased. Autopsy data showed that Dunn-sarcomas associated with amyloidoses occurred more frequently in the untreated mice.

Alterations in the intestinal microvillous surface area during the whole life span of the female rat ileum.

The present EM morphometric analysis is a continuation of a series of studies in which the changes of the microvillous surface area of the small intestine was investigated in the course of the entire life span of the female rat. It was concluded from the present data that the alterations of the ileal microvillous surface area are more balanced in the young, pregnant, lactating, adult, old and senile animals than that was observed in the case of the duodenum and jejunum. Positive correlations were found between the parameters height and surface area and, density and surface area measures of the microvilli. Microvillous width and density revealed an inverse relationship mainly in the case of the young and adult animals.

Pathophysiological changes of the cochlea during ageing--a review.

Research of the pathophysiology of the age-related human presbycusis was largely initiated by those investigations in which the cochlea's damages were experimentally induced by various acoustic exposures. It became apparent that the outer hair cells are more vulnerable to different noise influences than the inner hair cells. On the other hand, the role of the altered ultrastructural elements of various types, cannot be ruled out. The evolving of the age-related presbycusis was to a great extent established using large-scale model experiments, including mainly rodents. It seems that the age-bound presbycusis (cf. intrinsic degeneration of the cochlea) begins at the apical regions which will be later more worsening by various extrinsic traumas. It is suggested that the damages gradually taking part in the inner ear structures are bound to the age-dependent processes in which the ever-increasing formation of cross-linkages plays an important role as ageing progresses.

Morphometric changes in the duodenal microvillous surface area of the non-pregnant, pregnant and lactating female rat.

In the present study an attempt has been made to describe the morphometrical changes occurring in the microvilli of the duodenum of rats of different ages and periods of reproduction. The data showed that the microvillous surface area in the duodenum was greatest in senescent rats and lowest in adult and old animals. The values for lactating rats were similar to that for the senescent group. There was a direct correlation between the microvillous surface area with the height and density. By contrast, however, there was a negative correlation between the width and density of the duodenal microvilli.

Biological changes and diseases in aged CBA/Ca mice.

Cold adaptation, apparent protein metabolism, life span, body and organ weights, organ indices, mitochondrial changes in the lymphocytes, and frequency of diseases were examined in 661 (untreated) inbred CBA/Ca male mice. The rectal temperature proved to be lower in aged mice, i.e. the rectal temperature of old animals immediately after cold exposure was more distinctly decreased than that of young ones. The apparent protein metabolism measured by 75Se-selenomethionine turnover showed that biological half-life (T 1/2) values in the aged are almost linearly elevated. In very old animals the values are decreased. Body weight decreased significantly and continuously, spleen and liver indices decreased and heart index increased with age in healthy animals. The number of diseased animals increased with age peaking at the age of 751-900 days. After 900 days the number of diseased animals decreased. The most frequent diseases in the old animals are: hepatocellular carcinoma, amyloidosis and pulmonary adenocarcinoma. The mitochondria of spleen lymphocytes showed degenerative changes not associated with diseases, thus they can be considered as age-related biological changes.

Density of substance P, vasoactive intestinal polypeptide and somatostatin-containing nerve fibers in the ageing small intestine of the rats.

Immunoelectron microscopic investigations were carried out to study the substance P, vasoactive intestinal polypeptide (VIP) and somatostatin immunoreactive nerve elements in the wall of the small intestine. In young and old animals a large number of immunoreactive nerve fibers were found in all layers of the small intestine. They were observed closely to the epithelial cells, to the blood vessel basement membrane and to the smooth muscle cells and in some cases they were observed in a synapse with other unlabelled nerve fibers. On the other hand, in the senile animals very few immunoreactive nerve fibers were observed, calculated for a 100 micron2 tissue area. In the senile animals the overall number of nerve fibers was decreased in comparison to the young and old animals and most of them were in degeneration. This change could be the cause of the changes in the senescence-related epithelial transport processes and furthermore, of the modifications of the overall intestinal motility of the gastrointestinal tract, resulting in the age-dependent transit rates.

[Determination of ABO blood group markers in single hair segments]. / Bestimmung der ABO-Blutgruppenmerkmale am Einzelhaarsegment.

Determination of ABO-blood group on human hair segments of 79 individuals was performed by means of modified Yada absorption-elutions technique. The studies were carried out with 4 micron thin cross sections of hair. In 79% of the cases it was possible to establish the correct blood group. Individual hair segments of 0.5 cm length yielded reliable results. Antigen identification was best with blood group B and most difficult of the AB type.

[Immunoenzyme AB0 blood group determination using a single hair. I]. / Immunenzymatische AB0-Blutgruppenbestimmung am Einzelhaar. I. Mitteilung.

The immunoenzyme technique was used to determine the ABO blood group of strands of human scalp hair. The hair was obtained from 168 individuals of known blood groups (A1: n = 58; A2: n = 11; B: n = 28; O: n = 46; A1B: n = 16; A2B: n = 9). Immunostaining was carried out by using monoclonal anti-A, anti-B and anti-H as primary antibodies. Group-specific staining was clearly observed within the medulla of the hair. The ABO blood group of all hair samples was determined correctly by the Sternberger (PAP) or APAAP (immunoalkaline phosphatase) technique. The present study indicates that immunoenzyme techniques can be regarded as practical methods for determining ABO blood group of hair.

Changes in the intestinal microvillous surface area during reproduction and ageing in the female rat.

A morphometric study has been undertaken of the changes that occur in the microvillous surface area of young, pregnant, lactating, old and senescent rats. It has been shown that the microvilli are organelles with a quite stable conformation and that they exhibit no large scale dimensional changes throughout almost the entire life span. Lactation, however, does induce an apparent increase in microvillous surface area which may be associated with the significant changes which occur to the structure of the villus during reproduction in the rat.