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Survival and disease patterns in C57BL/6J mice subjected to undernutrition
Authors:K.E. Cheney  R.K. Liu  G.S. Smith  R.E. Leung  M.R. Mickey  R.L. Walford
Affiliation:1. Departments of Pathology and Biomathematics, University of California, Los Angeles, CA 90024, U.S.A.;2. University of California, Los Angeles, CA 90024, U.S.A.
Abstract:This study reports survival and disease patterns in a long-lived mouse strain subjected to undernutrition. Four cohorts were studied, each composed of two or more groups of mice, each normally-fed or restricted either pre- and/or postweaning. Restriction prior to weaning was effected by limiting access to the mother. animals restricted postweaning received a nutritionally complete diet, including a normal complement of vitamins and salts, but were fed only 4 portions/week vs 7 portions/week for those animals normally fed—hence the term under-nutrition to differentiate between this and malnutrition.Comparisons of disease patterns among groups revealed that the incidence of lymphoma, the most prevalent tumor, was uniformly decreased in the groups restricted postweaning, with or without preweaning restriction. In the last cohort, deaths of animals with lymphoma were shifted to later ages in the restricted groups, compared with the normally-fed controls.Whereas the lymphoma pattern was considerably modified by undernutrition, the effect on overall survival did not seem as dramatic. Gompertzian parameters for survival past 120 weeks were not statistically different, although with one exception, maximum survival and one of the Gompertzian parameters was consistently greater in groups restricted postweaning, compared with those restricted preweaning only, or not at all. Maximum survival is a parameter not unduly influenced by environmental factors such as infectious disease; consequently, this represents a meaningful effect of undernutrition.Statistically, more significant differences in tumor patterns than in survival suggests that the former are more sensitive to undernutrition than is the latter—at least in this strain of mouse. Greater lifespan prolongation in the restricted animals may be possible through better “fine tuning” of the diet, including improved portion control, particularly in the early postweaning period, to prevent rapid weight gain, and possibly through changes in dietary composition. Finally, it is suggested that undernutrition may exert its effects through an alteration in gene expression.
Keywords:To whom reprint requests should be addressed.
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