Date of Award


Degree Type


Degree Name

Doctor of Philosophy



Major Professor

Roy E. Beauchene

Committee Members

Jane R. Savage, John T. Smith, Mary Jo Hitchcock, Mary Rose Gram


The effects of dietary free radical inhibitors and of feed restriction on selected age associated biochemical parameters and on life span of AKR male mice were investigated. The control animals (n = 58) were fed a nutritionally adequate basal diet ad libitum; the restricted mice (n = 40) were allowed the basal diet 15 hours out of every 48 hours; the BHT (n = 40) and the vitamin E mice (n = 40) were fed the basal diet containing either 3 meq of butylated hydroxytoluene (0.33%) or dl-α-tocopheryl acetate (0.71%), respectively, per 100 g of feed.

One-half of the animals in each of the dietary groups was used for longevity studies; biochemical measurements were performed on the survivors of the other half of the mice at 12-months of age when approximately two-thirds of the controls were dead. Biochemical measurements were also performed for comparative purposes on 3-month and 6-month old mice eating the basal diet ad libitum.

The BHT and restricted mice consumed less feed and were smaller in body size than the controls, the reduction in feed intake being 5 percent and 33 percent, respectively, and the reduction in body weight being 9 percent and 19 percent, respectively, at 30 weeks of age.

The serum cholinesterase activity was significantly higher in 6-month, restricted and BHT mice than in the 12-month old controls. The BHT mice had a significantly higher liver catheptic activity than the control mice, while the values of the 3-month, 6-month and restricted mice were significantly lower than that of the controls. The catheptic activity of mice diagnosed as having leukemia was significantly higher than that of non-leukemic mice regardless of diet. Kidney succinoxidase activity was not significantly influenced by age or diet.

The percent acid soluble collagen of the skin was significantly higher in the 3-month, 6-month and restricted animals than in control mice. The in vitro lipid peroxidation of brain homogenates of only the vitamin E mice was significantly lower than that of the controls.

The mean life span of the mice fed the basal diet ad libitum was 336 days. Feed restriction increased the mean life span to 403 days and reduced the incidence of death due to leukemia. Vitamin E did not have a significant effect on either life span or the incidence of leukemia; on the other hand the BHT mice showed a marked tendency towards an extension of mean life span and a reduction in the incidence of death due to leukemia. The latter findings were attributed to the slight degree of self-imposed feed restriction observed in these animals. There was a significant negative regression of life span on growth rate, and when life span was adjusted for growth rate there was no difference in the estimated longevity of the four dietary groups.

Thus, feed restriction increased the mean life span and influenced the biochemical parameters in such a way that, in general, they resembled the values obtained for the chronologically younger animals. On the basis of these observations it was concluded that dietary free radical inhibitors per se did not increase life span but their effect was mediated via the mechanism of feed restriction.

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