Prenatal exposure to a maternal low protein diet shortens life span in rats

Background: Postweaning diet restriction is associated with prolongation of life span, reduced age-related disease and slower ageing. The effects of d iet restriction imposed prior to weaning have not been so well characterise d, but studies suggest an opposite effect with increased age-related diseas es occurring in offspring exposed to undernutrition in prenatal life. It re mains unclear whether life span is similarly adversely affected by early di et restriction. Objective: The present study in rats aimed to evaluate the impact of a maternal low protein diet upon the life span of the resulting o ffspring. Methods: Rat darns were fed either a 180-gram casein/kg control d iet or a 90-gram casein/kg low protein diet from conception until the end o f pregnancy. The offspring were then maintained with minimal handling until death from natural causes or distress-necessitated euthanasia. Results: Th e average life span of female rats exposed to low protein diets in utero wa s reduced by 11% (p = 0.044, Kaplan-Meier analysis). There was a similar bu t nonsignificant trend in the male offspring (control 76 +/- 3 weeks, low p rotein 73 +/- 3 weeks). In addition the rats exposed to a prenatal low prot ein diet had significantly higher systolic blood pressure at 4 weeks of age and tended to be smaller than control animals in postnatal life. Conclusio n: The results suggest that intrauterine diet restriction reduces life span in rats and contrasts with the well-recognised increase in life span produ ced by postweaning diet restriction. The timing of the nutritional interven tion appears to be critical and recognition of th is is relevant to underst anding the mechanisms underlying the effects of diet restriction on ageing and life span. Copyright (C) 2001 S. Karger AG,Basel.