CALORIE RESTRICTION REDUCES ULCERATIVE DERMATITIS AND INFECTION-RELATED MORTALITY IN P53-DEFICIENT AND WILD-TYPE MICE

Citation
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
Citations number
45
Categorie Soggetti
Dermatology & Venereal Diseases
ISSN journal
0022202X
Volume
111
Issue
2
Year of publication
1998
Pages
292 - 296
Database
ISI
SICI code
0022-202X(1998)111:2<292:CRRUDA>2.0.ZU;2-P
Abstract
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.