Effects of Genotype and Diet on Age-Related Lesions in Ad Libitum Fed and Calorie-Restricted F344, BN, and BNF3F1 Rats

The effects of calorie restriction (CR) on age-related lesions in Brown Norway, Fischer 344, and BNF3F1 hybrid rats are presented. A logistic regression analysis of data from histologic samples from rats of each genotype, sex, and diet at 12,18, 24, 30, and 36 months of age demonstrated the effects of age, diet, and sex on lesion prevalence in all three genotypes. CR reduced the prevalence of neoplastic, nonneoplastic proliferative, and degenerative lesions. All genotype-sex-age cohorts demonstrated a reduced average lesion burden with CR. Importantly, some lesions common to Brown Norway rats seldom occurred in Fischer 344 rats and vice versa. Some lesions that occurred in only one parental strain also occurred in BNF3F1 rats. Many traits occurred in all three genotypes but at significantly different prevalence rates. We suggest that the diseases and lesions that rats develop as they age are controlled by genes and environmental factors such as CR.