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Biomedical subjects

G Hofecker

Publications and source records attributed to G Hofecker.

At least 19 recordsLinked to original sources

[Results of experimental gerontology with respect to biological age].

Biological age may be defined as the state of the organism as a whole which is characteristic of the respective chronological age. Objective estimates of biological age are usually obtained by multiple regression analysis of a greater number of age parameters. However, this procedure should be based on a firm knowledge of the regularities of multicellular ageing. By means of a long-term study in male rats regularities of biological ageing have been demonstrated using multiple regression analysis, factor analysis and discriminant analysis. The multiple regression model pointed to an exponential relation between chronological and biological age. By factor analysis it has been shown that the change of the parameters represents to various extents primary ageing and system-specific secondary ageing. The results of discriminant analysis reveal a change in the ageing pattern during senescence. Consequently, test batteries for the objectivation of influences on the rate of ageing should be adapted to the respective phase of ageing in order to obtain maximum sensitivity.

Aging

Changes of DNA repair mechanisms during the aging of the rat.

Recent studies have shown a significant reduction in DNA repair capacity in aging rats. Therefore we were interested in investigating which repair mechanism is concerned in this reduction. We investigated: excision repair (ER); single-strand break repair (SSBR); double-strand break repair (DSBR); and gamma-endonuclease susceptibility (ES) by means of the following methods: [3H]thymidine ([3H]dThd) incorporation into DNA after damage by N-methyl-N-nitrosourea (MNU); nucleoid sedimentation after damage by methyl methanesulfonate (MMS); neutral elution techniques after damage by 4-nitroquinoline-1-oxide (NQO); and determination of ES sites by velocity sedimentation in an alkaline sucrose gradient after damage by gamma-irradiation. Studies were done with male Sprague-Dawley rats aged 9, 18 and 28 months using nine different organs. We were able to determine a distinct age dependency of excision repair, a slight reduction of single-strand break repair, an elevation of gamma-endonuclease susceptible sites and no significant change in double-strand break repair in the course of aging. Therefore we see a shift in the pattern of DNA repair: in old age strand break repair mechanisms become more important, while repair replication is reduced. From this we can conclude that genetic expression is altered during the aging process, with all the consequences for the disposition toward certain diseases.

4-Nitroquinoline-1-oxide

The influence of persistent crowding on the age changes of behavioral parameters and survival characteristics of rats.

One hundred fifty-six male Sprague-Dawley rats were submitted to crowding (12 rats/Makrolon-IV cage) from an age of 5 months onwards. An equal number from the same age cohort served as a control (6 rats/Makrolon-IV cage). As part of an age-test program, behavioral parameters (spontaneous motor activity, reactive motor activity and maze-learning ability) were measured at various ages between 8 and 30 months. The rats were sacrificed for additional measurements after the behavioral tests. Survival curves and age-specific mortality rates were calculated for those rats which died spontaneously in the course of the study. Control rats showed a significant decrease in spontaneous motor activity after an age of 18 months. Reactive motor activity of the controls revealed a fall in the number of large movements between 9 and 15 months, whereas the number of small movements increased up to an age of 30 months. Crowding conditions increased significantly both spontaneous and reactive activity. Maze-learning ability declined significantly with age in the controls whereas crowded rats revealed a tendency to better performance which seemed to be submitted to a seasonal rhythm. Crowded rats showed an improved survival characteristic, beginning at an age of 700 days. Mortality curves turned out to be distinct and parallel by straight line regression. It has been concluded that the positive effects of crowding on behavioral parameters and survival could be attributed to a decrease in vulnerability rather than to a lowered rate of aging.

Aging

The physiology and pathophysiology of ageing.

Ageing is a physiological process which impairs vitality and ultimately leads to death. It is found in all differentiated multicellular organisms. Recent theories attribute ageing to an accumulation of errors as the capacity of mechanisms for their repair and compensation becomes limited. Erroneous processes leading to ageing and death stem mainly from the protein-synthesizing machinery of the cell. At present, three types of hypotheses to explain ageing are under consideration. These are (1) the limited stability of genetic information, (2) a restriction in the availability of genetic information and (3) the liability to error of the information flow in protein synthesis. Recently, increasing interest has also been shown in certain post-synthetic changes in biological molecules which may impair cell functions. However, ageing cannot be explained entirely at the molecular and cellular level. Since it has been shown that faults may also emerge at the higher organizational levels of multicellular organisms, it is necessary to study ageing processes at various levels, taking into account the specific type of order innate in living organisms. The relationship between ageing and disease is characterized by increased morbidity and accompanied by an increasing chance of dying from certain diseases. The following events may be of major importance: (1) the progressive loss of specific order ('bionomic order') which leads to a reduced capacity of adaptation, compensation and repair; (2) continuous changes of the organism throughout life ('biomorphosis') which lose their usefulness after the attainment of maturity and promote pathological changes; (3) the long term accumulation of low-level noxious influences which increase the chance of becoming ill as age advances.

Adolescent

[The influence of persistent crowding on the spontaneous motor activity of the aging rat (author's transl)].

In the course of a long-term cohort study of stress and aging, the spontaneous activity of 169 male Sprague-Dawley rats was measured at various ages from 9 to 30 months. 84 animals were submitted to crowding from the age of 5 months onwards by housing them in groups of 12 per Makrolon-IV cage. 85 rats, kept as usual in groups of 6 per makrolon-IV cage, served as a control. Spontaneous activity was assessed by an electronic instrument (Animex Activity Meter), which also enabled us to distinguish between total and large movements. During senescence, the spontaneous activity of the control animals decreased slightly by approximately 20% after the age of 18 months. In addition to the quantitative change, a progressive flattening of the activity rhythm was observed. The animals kept under crowded conditions did not reveal any age-related decrease in spontaneous activity. At an advanced age, this resulted in significantly higher activity values in the crowded group as compared with the controls. The differences appeared even earlier and seemed to be more pronounced in the number of large movements. However, the progressive disappearance of the endogenous rhythm was apparent in both the crowded and the control group. It can be concluded that at least two types of change in the central nervous system may be responsible for the aging-changes in spontaneous activity: one which disintegrates the "time structure" of the organism, and a second one which affects motivational centers. Crowded conditions seem to improve the latter, whereas they have no effect on the aging of the "biological clock".

Age Factors

[The model in experimental gerontology (author's transl)].

In experimental gerontology as a biomedical science, the knowledge and understanding of aging is expressed in hypotheses, theories and models. In this context, the model turns out to be a specific criterion of a definite level of abstraction. The general concept of models comprehends three characteristics: illustration, reduction and pragmatism. Every model is an approximating attempt to comprehend reality. In experimental gerontology various kinds of models can be used. This variety is necessary result of the variety of methods used in this field of science. Any reductionism would imply a restriction, limitation and rigidity. The final aim of experimental gerontology should be the evaluation of a universal dynamic model of aging which is valid for any aging process in biological systems.

Aged

[Circadian studies with young and old rats (author's transl)].

8 and 28 months old, male Sprague-Dawley rats (36 animals in each group) were used to determine the rectal temperature, various organ weights (referred to the body weight and the brain weight), various blood parameters and the concentration of Ca and Mg in the plasma and the myocard as a function of the time of the day. The values were approximated to the function y = M + A cos (omega t + phi) (y = parameter value, M = mesor, mean value of the day, A = amplitude, omega = angular velocity, t = hour of the day, phi = acrophase, when y has its highest value). The approximations were significant at 6 out of 45 parameters in both groups (rectal) temperature, pancreas weight related to the body weight, leucocyte number/mm3, GPT, Mg and Ca/Mg in the plasma). 17 parameters could be approximated only at the young rats, 1 parameter only at the old animals. In some cases large age correlated alterations of the amplitude could be observed. The mesor changed only at the pancreas weight related to the body weight. The acrophase shifted only at the leucocyte number/mm3. These variations can lead to wrong interpretations when only mean values are used for age comparisons.

Aging

[Aspects of stress and aging in the rat (author's transl)].

Sprague-Dawley rats aged 6 to 22 months were stressed for 2, 16 and 9m resp. by the influence of noise (106 dB, 2h/d) and overcrowding (12 rats/Makrolon-IV-cage). Parameters of the plasma, brain, testicles and the liver (enzymes, metabolites and hormones) and well-known age parameters were evaluated to obtain objective criteria for stress influences. The weights of the whole body and some organs were also measured. The most distinct changes were seen in the plasma enzyme activities CPK, ALD, CHE and AP, in the concentrations of CHO and TRG and in the levels of testosterone, corticosterone and aldosterone. The contraction-relaxation of the tail tendon and the soluble collagen of the corium changed in the direction of higher age, just as lipofuscine content in the brain, cerebellum and the adrenals did. Some activities of enzymes and concentrations of metabolites changed in the brain, liver the testicles. Adrenal weights rose sharply in both stress groups; the body weight was lower. There were some differences in the effects of the two stress factors. These investigations gave some information about the relation between stress and aging and provide a simple means of determining the influence of stress.

Aging

[Gerontological pilot study on learning ability and memory in the stressed rat (author's transl)].

The influence of noise and overcrowding on the learning ability and memory was investigated during a long term cohort study in 120 male Sprague Dawley rats covering an age range from 8 to 14 months. The investigations were performed by means of a semi-automatical multiple-T-maze with 7 choice points. The results showed that noise and overcrowding enhanced the learning ability and memory in rats up to an age of 10 to 12 months. However, the learning ability and memory were declining faster with age in the stressed animals than in the unstressed ones. The stressor "overcrowding" proved to be more effective than the stressor "noise" applied by the authors.

Aging

[Discriminant analysis of age parameters of the rat (author's transl)].

The capacity of age parameters to discriminate between groups or individuals of different biological age was investigated in the course of a long-term cohort study. 23 age parameters measured in 71 male Sprague-Dawley rats at the ages of 10, 17, 25 and 30 months, were submitted to a stepwise discriminant analysis. An optimal simultaneous discrimination between the four age groups was obtained by 3 discriminant functions with scores of 89.8%, 6.2% and 4%, with a correct classification of 98,6% of all individuals. Three analyses of successive age groups (10--17, 17--25, 25--30 months) resulted in a 100% correct classification by one function each. However, it turned out that in different phases of senescence an optimal discrimination between individuals or groups of different biological age is obtained by distinct combinations and weights of the parameters.

Aging

[Problems of the assessment of biological age (author's transl)].

Biological age may be defined at the state of the organism as a whole which is characteristic of the respective chronological age. Usually, it is estimated by multivariate analysis of a battery of age parameters. However, this procedure requires the knowledge of the regularities of multicellular ageing since interferences about the behaviour of the total system from its subsystems may only drawn when the regularities of the total system are understood. By means of the ageing of the rat, the possibility is demonstrated to study these regularities by factor analysis. As a result, primary and system-specific secondary aging processes are postulated which are expressed to various extents in the individual age parameters.

Aging

[Perspectives in experimental gerontology (author's transl)].

Experimental gerontology is changing progressively from an idiographic (descriptive) science to a nomothetic (conceivable in terms of laws) one. Besides the punctual studies of the total complex of aging, those investigations will acquire increasing significance which take into account the bionomal character of life. In addition, the views of logic science, epistomology and system theory will be employed in experimental gerontology more often than is the case now. Experimental gerontology will finally lead to the development of a theoretical gerontology.

Aged