Sn. Perkins et al., CALORIE RESTRICTION REDUCES ULCERATIVE DERMATITIS AND INFECTION-RELATED MORTALITY IN P53-DEFICIENT AND WILD-TYPE MICE, Journal of investigative dermatology, 111(2), 1998, pp. 292-296
In rodents calorie restriction (CR) reduces cancer incidence, improves
health by delaying age-related declines in physiologic measures, and
extends both median and maximal life span. The mechanisms underlying t
he various beneficial effects of CR remain undefined. In this study, h
eterozygous p53-deficient (p53(+/-)) mice (in which the inactivation o
f one allele of the p53 tumor suppressor gene increases susceptibility
to spontaneous and carcinogen-induced tumor development) and wild-typ
e (WT) litter mates were subjected to a two-stage skin carcinogenesis
protocol with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylpho
rbol-13-acetate. Instead of skin carcinomas however, the chemical trea
tment protocol caused ulcerous skin lesions, and 89% of mice fed ad li
bitum died from infection/septicemia. When WT mice were restricted to
60% of the average calorie intake of the respective ad libitum group,
however, only 33% developed such lesions, and the CR mice survived tu
ice as long on average as the ad libitum mice. CR also extended life s
pan in p53(+/-) mice, but 50% of p53(+/-) mice subjected to CR still d
eveloped skin ulcers and mean life span was shorter than that seen in
WT mice. Differences in response to CR between WT and p53(+/-) mice ma
y be due to the reduction in p53 gene dosage, dissimilarity in the app
lication of the CR treatment, or both. These results suggest that some
of the beneficial effects of CR may need full expression of p53 for c
omplete realization.