M. Skalicky

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.

Investigations on the kinetics of collagen-metabolism in young and old rats

Abstract Collagen is one of the most important body-proteins (about 30%) whose structure, function and turnover depends on certain diseases and on the aging process. After designing a general model of collagen-metabolism the course of the specific activity of hydroxyproline in three different collagen-modifications of skin and tail-tendon was investigated for 32 days in Sprague-Dawley rats with an age of 3 resp. 20–24 months. These modifications are typical for the structure of collagen. From this course and from the specific activity in blood and urine the turnover rates of one single modification into one another were calculated. From the size of these determined constants conclusions could be drawn upon the different ways of collagen-biosynthesis in young and old animals. Moreover this model should give information about the nature of this way of collagen-synthesis in different diseases of connective tissue.

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.

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.

Nonenzymatic Glycosylation of Collagen as a Model of Posttranslational Aging

At the very beginning of experimental gerontology, Verzar (1957) put forward the idea that macromolecules with no or a slow turnover are altered irreversibly with time and, consequently, age. His favorite model of this posttranslational age-related change was the aging of the tail tendon collagen of the rat. Throughout life, tail tendon collagen shows a progressive increase in rigidity, accompanied by a rising resistance to thermal and chemical degradation.