[Kinetics of the metabolism of collagen in young and old rats (author's transl)].
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Biomedical subjects
Publications and source records attributed to H Niedermüller.
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Two groups of 60 male Sprague-Dawley rats aged 3 and 20-24 months respectively were used to establish a 3-compartmentmodel of the kinetics of the collagen metabolism in the tail tendon and skin by means of tritium labelled L-prolin. The 3 compartments were divided into pro- and tropocollagen, labile polymer collagen and stabile polymer collagen respectively. The results suggest the following conclusions concerning the metabolism and ageing of the collagens investigated: 1. Collagen of the tendon and collagen of the skin reveal different dynamics of metabolism. 2. Stabile and labile polymeric collagen originate from different tropocollagens. 3. Both intracellular and extracellular processes are responsible for the age-changes of tendon- and skin-collagen.
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We tried to develop a model of in-vivo investigations into the DNA repair capacity of rats and, by means of this model, to determine the effect of age. To this end the DNA repair capacity was determined after gamma-irradiation with 3 groups of male white Sprague-Dawley rats aged 6, 18-20 and 32-34 months. The organs liver, kidney, heart and spleen were used for this investigation. The relative repair (RR) showed a discontinuous course both in the 4 organs, and in the 3 different age groups. We define "relative repair" as the relationship between the specific activity of DNA decomposition products and the specific activity of DNA in an irradiated test group, as compared with an unirradiated control group. In all age groups the course was similar in the liver and the spleen, especially in the young rats, as well as in the heart and the kidney. Age differences were seen to be significant in all 4 organs at particular intervals after the irradiation, which means that the maximum relative repair occurs at different times. The integration over the whole course of the investigation shows a distinct reduction in the relative repair with increasing age in all the investigated organs except the spleen, where we could not see a difference between the 2 older groups.
Stress-strain diagrams of standardizised longitudinal and transversal stripes of the thoracic aorta of 125 male Sprague-Dawley rats aged 9, 15, 24 and 30 months were recorded by an electromechanical instrument. The stripes were subjected to three successive extension-relaxation cycles. The relaxation curves of the third cycle were approximated to the functions y = a + bx and y = cxd (longitudinal stripes) and y = mxf and y = gxh (transversal stripes) respectively. The parameters could be interpreted as measures for structural and functional properties of elastic and collagenous fibers. The age changes of the curve parameters led to the following conclusions concerning age-dependent functional alterations of the aorta: The emphasis can be placed upon the increasing resistance counteracting the extension occuring with great stroke volumes. This may lead to the reduction of the capacity of the air chamber with great stroke volumes. These phenomena seem to be mainly caused by an increase of the pitch of the spiral of the collagenic fiber and the increase of the amount and/or the stability of the collagen. Age-related alterations of the elastin and of the net structure formed by the fibers influence also the distensibility at smaller extensions but seem to be less important. Therefore, the structural alterations of the aorta with age will affect the function in the first place at large stroke volumes and not be very obvious at a basic heart performance.
The motor activity as an behavioural parameter provides information about the functional state of the organism as a whole. Therefore it is an important age parameter. The results of activity measurements, however, depend strongly on the method of registration. Using 3 groups of male Sprague-Dawley rats aged 9, 15 and 29 months two methods have been tested: 1) An electronic recording: the rats were registrated in their normal cages on the Animex-Activity-Meter during the dark-phase in complete darkness. The activity measured by this method has been regarded as spontaneous activity. 2) A kinematographic method: the rats were registrated in a changed environment at constant light during the dark-phase. The activity assessed by this method has been regarded as reactive activity. Spontaneous and reactive activity show a different age dependence. For the use of the motor activity as an age parameter, both, spontaneous and reactive activity, should be assessed to get a better information about the ageing of the different functional levels of the systems governing the animal's behaviour.
Using 136 male Sprague-Dawley rats of various ages, the ageing functions of parameters originating from different organisation levels of the organism were determined. The parameters which were investigated on different levels show a non linear time dependence which can be approximated by simple or composed exponential decay-functions or by rising logarithmic functions. The results suggest a logarithmic relation between biological and chronological age.
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Preliminary results of a long-term study on 1100 male Sprague-Dawley rats are presented, showing the influence of running exercise, of restricted diet, of both of these together and of the s.c. application of lypholized testis cells. Up to now animals aged 9, 15 and 24 mths were investigated. The test-animals were exposed to the experimental conditions from their 6th month of life. The running exercise was carried out on a treadmill (30 m at a speed of 25 m/min, horizontal) 5 days a week. A food restriction of about 20% was achieved by 2 fasting-days a week. The lyophilized testis cells were injected for the first time at an age of 9 mths and afterwards in 6 mths intervals. Between the injection and the assessment of the age-parameters there was an interval of 6 mths. S o fare the following parameters of the comprehensive test-program have been evaluated: 1) running performance in m (treadmill, 20 m/min, ascent 15 degrees), 2) motor activity (Animex Activity Meter), 3) chemical contraction-relaxation of tail-tendon-fibers, 4) total lipids and total cholesterol in the plasma. The results obtained so far show that a mild regular training, moderate food restriction and the s.c. application of testis-cells are able to cause a significant shift in the dirction of a younger biological age in at least some of the age parameters. The action of the testis-cells seems to affect most of the age parameters but shows the tendency to be more distinct at a higher age. More concrete statements about the influence on the biological age or the vitality will only be possible after the multivariate analysis of the results.
II. Elasticity Parameters in Various Ages Power-extension diagrams of longitudinal and transversal stripes of the Aorta thoracica were recorded by means of an elctro-mechanical measuring instrument. The samples were taken from 108 male Sprague-Dawley rats aged 9, 15 and 24 months. The following parameters describing age-dependent alterations were calculated from the hysteresis loops of three consecutive extension-relaxation cycles: 1. the maximum power 2. the area of the first hysteresis loop 3. the characteristic of the relaxation-part of the third cycle. The maximum power and partly the areas of the hysteresis loops increased with age. The curves obtained by longitudinal stripes were approximated to a linear function (y = a + bx) plus a power-function (y = cxd). Their constants were explained as indices to the plasticity of the aorta, the retraction-power of the elastic fibres, the degree of the spiralization of the collagen fibres and the amount and/or the stability of the collagen. The ageing changes of these parameters indicated an increase of plasticity, an increase in the retraction-power of the elastic fibres, a rise of the pitch of the collagen spiral and an increase in the amount and/or in the stability of collagen. The curves from the extension of the transversal stripes revealed a different extension characteristic and could be described as the sum of two power functions. The causes of this different behaviour are not yet clearly understood.
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Five hours after a limited, nonhypotensive trauma without gross interference with coagulopathy, lungs of dogs were found to be completely deficient of heparin-releasable, metabolically active lipoprotein lipase. This indicates that the pathway of circulating lipoprotein triglyceride hydrolysis as a source of palmitate for pulmonary dipalmitoyllecithin synthesis is blocked post-traumatically. The possible significance of this finding on post-traumatic impairment of pulmonary surfactant synthesis and accumulation of fatty material in the pulmonary capillary bed is discussed.
Five hours after a limited, nonhypotensive trauma without gross interference with coagulopathy the lung of dogs was found to be completely deficient of heparin-releasable, metabolically active lipoprotein lipase.
The time course of the incorporation of radioactivity into the liver, kidney, heart, spleen, lung, adrenal glands, and testes following subcutaneous application of L-histidine-2,5-T-labelled homogenates of liver, kidney and heart has been measured in 105 male Sprague-Dawley rats aged 3 months (weight: x = 350 g). The homogenates had been prepared from organs of rats of the same age, sex and weight, each labelled with 400 muCi L-histidine-2,5-T. The maximal incorporation of activity from the homogenates into the organs investigated has been found 24 h after injection. In the kidney, however, an additional peak appeared already 5 h post applicationen. The comparison of the activities of the liver, kidney and heart, taking into account the differences in organ metabolism, revealed a significantly higher incorporation into the homologous than in the non-homologous organs. This specific incorporation appeared 2 h after the injection and could be found until about 24 h. The type of labelling, the method of sample preparation and the time of absorption allowed to conclude that the specific affinity to the homologous organs might have been due to a relatively small amount of short peptides. The functional significance especially for the regeneration of impaired organs has been discussed taking into account earlier results.
The possible transfer of learning performance by proteins and ribonucleic acids was studied. 140 male Sprague-Dawley rats aged 3 months and 68 aged 20 months were used. Proteins and ribonucleic acids were isolated from the brains of trained and untrained rats aged 3 months. The difference in learning performance was tested and the incorporation of the above-mentioned substances into the hippo-campus and the residual brain in the two age-groups was measured using radioactive labelled material. A specific transfer of learned information-contents on the molecular level was found only after transfer of proteins in both young and old rats; the results of the training are well correlated with those of the incorporation. The two age-groups differ especially with regard to the learning performance, expressed in the error number. In th older group the error number is significantly lower in contrast to the learning time, that is slightly shorter in the younger group. This can be explained by the differences between the incorporation of brain proteins of trained animals into animals of different age, as well as by the investigations of some authors, who distinguished between different modes of learning. The lower incorporation of labelled substance into the brains of old animals is remarkable; the conclusion is a lower turnover of these substances in the brain of old animals, especially of the ribonucleic-acids. Nevertheless the learning performance of complex information-contents is not impaired.
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The rate of metabolic kinetics and the frequency of biological cycles may be correlated with the rate of aging and the maximum life-span potential. Therefore, investigation either into changes with age of such parameters within one species or into differences between species may give some information about the genetic programming of the aging process. Male Sprague-Dawley rats aged 3.5, 7, 12, 17, 23, and 33 months (m) were used to determine the changes with age of those metabolic pathways mentioned in the title, using the liver (LI), kidney (KI), brain (BR), heart (HE) and the skeletal muscle (SM). The maximum percentage of glucose utilization via the pentose pathway, compared to the total glucose utilization, was calculated after intravenous administration of D-[1-14C]- and D-[6-14C]glucose by the determination of the trioses (as lipids) 3 hours after the application. Furthermore, in rats aged 13 and 25 m the kinetics of both glucoses was measured in liver, kidney, heart, brain, skeletal muscle, spleen (SP), and testes (TE) during the first 3 hours after application. Pentose pathway values were calculated. The results indicate a decrease in the glucose utilization via the pentose pathway in the course of aging in liver, kidney, heart and skeletal muscle and a decrease from 3.5 months on in brain, younger rats exhibit a higher rate of glucose utilization via the pentose pathway as do old ones, the reduction of the pentose pathway may possibly be the cause of higher lipofuscin accumulation in the cells of some organs, lacking sufficient reduction equivalents for lipid metabolism.