It has been shown that life-long, regular physical exercise has benefits for humans as well as laboratory animals. Population studies have shown that the longevity of humans is increased due to the decrease in all-cause mortality. Further, the functional capacities of organ systems, especially the cardiovascular, are maintained better. Body fat content stays lower. Similar conclusions have been drawn from animal studies, most of them using voluntary exercise in running wheels. We have previously shown that spontaneous activity, measured in an open field setting, is better preserved, suggesting a slowing of sensorimotor impairment with age, and possibly improved maintenance of dopaminergic and cholinergic systems. Further, the systemic effect on connective tissues was a slowing of the age-dependent increase of stability by changes in the cross-linking patterns. The purpose of the present investigation was to analyze whether late-onset training programs had any such effects, i.e., whether the aging effects seen in sedentary animals could be reversed to some extent. We trained male Sprague-Dawley rats from the age of 18 and 20 months until the age of 22 months, i.e., for 4 and 2 months, in a treadmill for 800 m/day. Spontaneous activity in an open field was assessed at the ages of 18, 20, and 22 months. For systemic changes in connective tissues, tail tendons were analyzed with respect to thermal stability and biomechanical strength parameters. The rats trained for 4 months lost weight significantly, which suggests that most of the fat accumulated during a sedentary life can be removed by physical exercise. Two months of training, either from the age of 18 or 20 months, had a positive effect on spontaneous activity, while the last 2 months of a 4-month training period had a negative influence. We conclude that the exercise program was too strenuous to be maintained for 4 months, which should be interpreted as a failure to increase the functional capacity sufficiently. Analysis of the thermal stability and biomechanical properties showed that both training programs moved these properties in a "younger" direction. We conclude that training starting late in life also influences the aging rat in a positive way, although there are limitations to the intensity of training that is beneficial.

Aging↗

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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.

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.

Aging↗

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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↗

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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.

Aging↗

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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.

Age Factors↗

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[Zinc metabolism in swine. 4. Distribution and dynamics in blood].

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Animals↗