Programming of hepatic antioxidant capacity and oxidative injury in the ageing rat

Exposure to undernutrition in fetal life increases the susceptibility of humans and animals to major disease states in adult life. Studies of rodents exposed to protein restriction during fetal life indicate that lifespan is reduced, a finding that is the opposite of the well-documented improvement in longevity noted with post-weaning caloric restriction. The maternal low-protein (MLP) model of rat pregnancy therefore provides a suitable vehicle to consider how nutrition in fetal life may programme mechanisms of ageing. Pregnant rats were fed control (n = 7) or MLP diet (n = 7) throughout pregnancy. At birth, increased oxidation of hepatic proteins was noted, and this appeared related to activity of glutathione reductase. Older offspring were studied at 4, 16, 30 and 44 weeks of age and analyses revealed that MLP exposure in utero produced sex-specific differences in oxidant:antioxidant balance. In male offspring, MLP increased protein carbonyl concentrations in the liver (P = 0.013) and increased glutathione peroxidase activity (P = 0.018). These programmed changes were absent in the female offspring. The data support the hypothesis that reduced lifespan in rats subject to prenatal protein restriction is a consequence of enhanced oxidative processes promoting apoptosis and loss of tissue function. Mechanisms of ageing appear to be subject to nutritional programming during early development.