Calorie Restriction Induces a p53-independent Delay of Spontaneous Carcinogenesis

We reported previouslythat calorie restriction (CR) delays spontane ous carcinogenesisin p53-deficient(pS3@) mice, suggestingthat CR modulates carcinogenesis by p53-independent mechanisms. To further evaluate the role of p53, we monitored tumor development in p53@ and wild-type (pS3@'@) mice fed ad libilum (AL) or a CR regimen (60% of AL calorie intake). CR delayedtumor mortalityin p53' and pS3@ mice (mean time to death, 169and 648 days, respectively) relative to AL feeding (104 and 470 days). The estimated age-specific cancer death rate AL:CR ratios were 4.3 for p53@ mice and 4.4 for p53@'@mice. Thus, despite the acceleratedonset of carcinogenesisin p53' mice,the tumor-delaying effect of CR was similar in the two genotypes.