[Studies on aging through analysis of the glucose metabolism related to the ATP--production of the senescence accelerated mouse (SAM)].

It is thought that the senescence accelerated mouse (SAM) strains are very useful for examination of the aging mechanism. In particular, SAMP8 is useful since this substrain shows age-related deterioration of learning ability. One of the most attractive hypotheses of aging is that aging is a result of long-term exposure to free radicals generated through the glucose metabolism, and it is possible that oxygen radicals might be involved in the aging mechanism of SAM. In the present study, to elucidate the relation between free radicals and aging acceleration in SAMP8, we examined the changes in food intake, body weight and spontaneous motor activity. Biochemical analyses of blood glucose, cholesterol, triglyceride, total protein and albumin in SAMP8 and R1 mice were also performed. In addition, the amounts of ATP, creatine phosphate (Cr-P) and lipid peroxide in the brains of SAMP8 and R1 mice were measured. As for SAMP8, an increase in food intake and a decrease in body weight and spontaneous motor activity were observed as compared with SAMR1 control mice. These results may indicate that energy metabolism is abnormal in SAMP8. The lipid peroxide level in the brain of SAMP8 at 3 months of age was significantly lower than that of the control mice. However, the ATP and Cr-P amounts in the SAMP8 brain were same as those in the control mice at the same age. These results suggest that generation of free radicals decreases due to lowered glucose metabolism and that the amount of ATP production in the brain of SAMP8 is lower than that of the control mice. In conclusion the aging of SAMP8 may result from a decrease of the glucose metabolism and of the utilization of ATP rather than from injury caused by free radicals induced through the glucose metabolism.