Dietary restriction alone and in combination with oral ethoxyquin/2-mercaptoethylamine in mice

To investigate effects of dietary caloric restriction (DR) combined with antioxidant feeding, long-lived hybrid mice were divided into four dietary groups at weaning, and followed until natural death. Groups "C" and "R" received control (97 kcal/wk) and restricted (56 kcal/wk) diets respectively. Groups "C+ alpha ox" and "R+ alpha ox" received C or R diets supplemented with an antioxidant mixture (2-mercaptoethylamine plus ethoxyquin). R mice (mean life span 41 months) significantly outlived the other three groups (mean life span 30-34 months). Hepatic degeneration and increased hepatoma in the R+ alpha ox group suggested unusual hepatotoxicity of this regimen. Antioxidants had little effect on splenic cell mitogen response in similarly fed mice sacrificed at 12-15 months. Gompertz analysis suggests that the beneficial effect of DR may be due to reductions in initial vulnerability or rate-of-aging parameters, or both, and that the relative influence of each factor may vary with animal strain and DR protocol used.