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H Niedermüller

Publications and source records attributed to H Niedermüller.

53 records · Page 3Linked to original sources

Models of the biological age of the rat. I. A factor model of age parameters.

The hypothesis of biological age postulates a fixed pattern in the aging of the multicellular organism. As a test of this hypothesis 23 age parameters of the rat were submitted to factor analysis. The data used in this study were a result of a long-term cohort study on 240 male Sprague-Dawley rats, which covered an age range of 10-30 months. The age parameters were obtained from various systems and levels of organization. The analysis revealed that there is a fixed pattern in the variations of the parameters. In this factor pattern the parameters are grouped into six factors, five of which can be attributed to the aging process. The first factor is interpreted as representing primary aging, factors 2-5 are interpreted as an expression of system-specific secondary processes of multicellular aging. Approximately 40% of the total variation of all parameters turned out to be random or due to processes other than aging.

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Models of the biological age of the rat. II. Multiple regression models in the study on influencing aging.

The study of influences on multicellular aging requires mathematical models of biological age (BA) as a standard against which deviations from "normal aging" can be measured. A long-term cohort study with initially 1100 male Sprague-Dawley rats served to establish multiple regression models of BA and to test the effects of fast days, physical training, a combination of fast days plus physical training, and the long-term action of subcutaneously applied lyophilized heterologous fetal testis material. All influences started after the attainment of maturity. The models were calculated on the basis of an exponential decrease in vitality during senescence. Twenty-three parameters from a total number of 42 were selected for a general model. By means of a factor analysis, the general model was subdivided into five factor models of BA to distinguish between primary and various types of secondary aging changes. All experimental conditions showed clearly detectable but not dramatic effects on the general model of BA in the sense of a revitalizaion. The most pronounced effect was found in the group pretreated with testis lyophilisate. The results obtained with the factor models suggest that this effect might be due to influences on primary aging as well as on some secondary changes.

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Assessment of modifications of the rate of aging in the rat.

Multivariate models of BA are, at present, the only way of measuring the main subject of gerontological research, namely, aging of the organism as a whole. Aging is obviously not a completely random process without any regularity, but shows a pattern which is determined by the organism's principles of order and its answer to the stochastic events of primary aging. Based on this theoretical concept, which is supported by results of factor analysis, multicellular aging may be described by a single complex variable, BA. However, the non-linearity of age changes and the different extent to which primary and secondary aging are involved, as well as factors other than aging, restrict the sensitivity of multiple regression models. Sensitivity may be increased by selecting parameters according to their discriminating power revealed by discriminant analysis. Wherever influences on aging are to be tested, a combination of the three types of multivariate methods will allow for an objectivation of effects and provide clues to a possible mode of action.

Journal Article↗

Age dependence of signal transduction and cell signaling as a major factor of intervention into the aging process.

Nowadays, it has become necessary to investigate the mechanisms underlying aging changes and their modulation. Of particular interest are the cellular and molecular level cell-cell and cell-matrix interactions. Thus, we partly determined in rats aged 9 and 31 months (a) the concentrations and the activities of signal molecules, such as G-proteins, cyclic adenosine monophosphate (cAMP) and kinases (cellular) and collagens, proteoglycans (PG) and fibronectin (extracellular) in vivo in the skin of the back, as well as in isolated fibroblasts and keratinocytes; (b) the cell proliferation and (c) we tried to retard the aging process in the skin by topical application (or by addition to cell cultures) of fetal mesenchymal cells, PGs, and soya matrix and we compared the above mentioned parameters with those obtained by stimulation of skin cells with growth factors. There are indications that there is (a) no change in the quantity of Gs-proteins but a reduction of the binding capacity. We found lower concentrations of cAMP, a reduced activity of protein kinase C in vivo, a higher collagen crosslinking, a lower PG concentration and no change of the amount of fibronectin in the old rat's skin and (b) there is a more or less extensive restoration of these parameters by all the above mentioned stimuli. So, we conclude that all the above mentioned influences modulate the aging process of the skin and its cells by intervention into the signaling pathways, by mediating new signals to the cells and hence by readjusting damaged feedforward systems in the cells.

Journal Article↗

The effect of aging on laboratory values in dogs.

The main objective of this study was to examine age-associated changes in laboratory values in dogs in order to establish standard values for dogs of a certain age. These standard values could serve to judge the health status of individual dogs and possibly estimate their remaining life expectancy. Thus, haematological and immunological parameters, plasma constituents, kidney characteristics and the capacity of homeostasis were determined in German shephard dogs (0.5-13.5 years) and beagles (4-9 years). Significant changes were noted. We detected that the number of white blood cells declines with age. The change in a number of organ specific enzymes indicates organ involution and increased cell death. Increased plasma glucose levels and a decreased glucose tolerance point to a diminished sensitivity of tissue to concentrations change due to a decrease in organ production and changes in the immune system, which are also reflected in an impaired lymphocyte proliferation capacity. These factors lead to an increased blood sedimentation rate. Cortisol increases might reflect a reduced stress resistance. Age-related decreases in aldosterone concentration and PAH-clearance were also found.

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The change in the supply with reduction equivalents in different organs of the rat during aging.

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.

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[Physiosclerosis of various blood vessels in the rat].

The rat is notoriously resistant to atherosclerosis, however, physiosclerosis appears to develop in the rat in the same way as in man. Since physiosclerosis is very likely to set the stage for the development of atherosclerosis, there must be a fundamental difference in physiosclerosis between man and rat. In an investigation of this difference, we analyzed stress-strain curves of the aorta and determined the lipid and calcium content of several blood vessels of male Sprague-Dawley rats at various ages between 9 and 33 months. Physiosclerosis was mainly due to an increase in the amount and rigidity of collagen with no sign of early elastolysis. Lipid concentration paralleled increasing plasma level only in early senescence and decreased after an age of 18 months. Calcium obviously accumulates at the same speed as in man, dependent on the chronological rather than on the biological age. In the short-lived rat it, therefore, does not reach the high levels found in man (Fleckenstein, 1983), which may trigger changes in smooth muscle cells related to the onset of atherosclerosis.

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[Is selection for extended life expectancy possible by regularity in aging?].

To answer this question it is important to explain the mode of development of the different maximum life span potentials (MLP) during evolution. We know by empiric-historical investigations, that at least later in evolution appearing species of mammals possess a higher MLP. What does then mean a "regular process"? The aging process is a regular one, being a physiologic event, in the character of that what all we can determine at it, as far as it allows explanation and prediction. This did succeed in a high degree during the until now short tradition of experimental gerontology. We refer to experimental results not only from the literature but also from our own work on repair, genetic and metabolic changes and multivariate investigations into the biological age, to decide from two hypotheses of the causes of aging, how the title question can be answered: a) aging as a programmed event, brought about by aging genes, controlled by an intrinsic clock. These genes should restrict life expectancy or the replicative capacity of cells--hence the adaptive hypothesis; b) aging as a consequence of the accumulation of errors counteracted by antibiosenescent strategies (AS)--hence nonadaptive hypotheses, the most plausible one being that of the disposable soma. Later species are adapted better to changing environmental conditions by their other development, their ecological niches are larger, their environment contains specifically lesser dangers and risks, because they better cope with them--therefore it is worth while to spend more energy for the maintenance of their soma than for their reproduction: they develop better and more AS.(ABSTRACT TRUNCATED AT 250 WORDS)

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[Education and graduate education in geriatrics and gerontology: current status in Austria].

Further education in practical, clinical and scientific-theoretical gerontology is of great importance either for the global care of the elderly or to increase the knowledge concerning the problems of aging. In this paper we try to evaluate critically activities referring to this, to furthermore develop in international comparison strategies to improve the situation. We present objectives of the Austrian health politics and we more precisely depict the actual implementation as to university and non-university education events.

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