Modulation of the ageing process in the rat

The elderly part of the population grows both in numbers and age, which increases the prevalence of chronic degenerative diseases. Life-long keeping of physical fitness and avoidance of overweight are important for preventing a number of age-related diseases. An active life-style also increases life expectancy. Results from studies on animals agree with these findings from population studies. The mechanisms behind the beneficial effects of physical activity and avoidance of overweight are, however, largely unknown. This project aims at extending from previous projects the analysis of the effects of life-long physical exercise and food restriction on the physiological ageing processes in the male rat from the age of 5 to that of 23 months. Since rats with free access to food grow obese with ageing, food restriction will be used as a model for avoidance of overweight. In the previous studies we found that physical exercise preserved certain nerve cells in the brain and kept spontaneous activity in an open field setting at a more active level. For this activity also food restriction was beneficial. Now these studies are extended with tests on learning and memory. The strength of bones was also affected by physical exercise. Further, a pilot project using material from these animals showed that a parameter for bone formation did not decline in animals which had run in running wheels. Bone metabolism will, therefore, be studied further measuring parameters for bone formation and resorption as well as characteristics for certain bone cells.. Also cell products of importance for bone metabolism will be analysed. Finally, bone mineral density will be measured. In the previous studies there were marked differences in survival between the different groups, with the exercising animals surviving best and the sedentary, fat animals having the highest mortality. The study of immunological parameters (also here the exercising animals had the best values) will be extended. Further, sympathetic activity and oxidative stress will be measured. The results may pave ways to new concepts in the pharmacological prevention of age associated diseases.

Major health problems are caused today by physical inactivity as well as by overweight. Epidemiological studies suggest that physical activity has beneficial effects on several age-related diseases as well as overall mortality while overweight causes serious health problems in the ageing Western populations. To study some of the mechanisms behind these effects we used the same animal model as in our previous projects P12474-MED and P13801-MED. One group of rats exercised voluntarily in running wheels from 5 to 23 months of age, while other groups were exercised in treadmills or kept lean or allowed to grow fat. The exercise in the treadmill and the voluntary use of running wheels can be seen as a form of enrichment of the rat`s environment. Cognitive abilities (learning and memory) were assessed with sensitive methods (the multiple T- maze and the Morris water-maze) for analysis of behaviour under standardized conditions. With ageing these abilities deteriorated. The important preventive factor turned out not to be physical exercise but training with the same methods at an earlier age. Osteoporosis in elderly men is a frequent and severe condition. The data of the present project on a rodent model of osteoporosis in elderly men show that age related bone loss results from an excessive bone resorption and concomitantly decreased bone formation. These results could lead to new pharmaceutical strategies for the treatment of osteoporosis in elderly men. We also found evidence for enhanced oxidative stress and reduced immune functions in the old compared to young animals. These results were not correlated with any changes in peripheral catecholamine levels. Importantly, the self renewal capacity of bone marrow derived hemopoietic stem cells (HSC) was significantly reduced, and this effect was weaker in animals voluntarily training in running wheels. Hence, a reduced quality of HSCs may contribute to age associated immune defects, and physical exercise may prevent this phenomenon. These results suggest further avenues for research developing interventions against major age-related diseases.