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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 diet restriction imposed prior to weaning have not been so well characterised, but studies suggest an opposite effect with increased age-related diseases occurring in offspring exposed to undernutrition in prenatal life. It remains unclear whether life span is similarly adversely affected by early diet 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 offspring. Methods: Rat dams were fed either a 180-gram casein/kg control diet or a 90-gram casein/kg low protein diet from conception until the end of pregnancy. The offspring were then maintained with minimal handling until death from natural causes or distress-necessitated euthanasia. Results: The average life span of female rats exposed to low protein diets in utero was reduced by 11% (p = 0.044, Kaplan-Meier analysis). There was a similar but non- significant trend in the male offspring (control 76 ± 3 weeks, low protein 73 ± 3 weeks). In addition the rats exposed to a prenatal low protein diet had significantly higher systolic blood pressure at 4 weeks of age and tended to be smaller than control animals in postnatal life. Conclusion: The results suggest that intrauterine diet restriction reduces life span in rats and contrasts with the well-recognised increase in life span produced by postweaning diet restriction. The timing of the nutritional intervention appears to be critical and recognition of this is relevant to understanding the mechanisms underlying the effects of diet restriction on ageing and life span.