Understanding the molecular mechanisms by which maternal diet influences longevity

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The diet of an individual has an important influence on the health of an individual at any stage of life. However there is evidence to suggest that the diet of a pregnant woman is particularly important as it has major long-term consequences on the health of her baby many years later when they themselves are adult. Babies that are not well nourished during pregnancy often have a low birth weight. It has been shown that individuals with a low birth weight are not only less likely to survive delivery but are also at substantially increased risk of developing various common diseases such as diabetes, high blood pressure and heart disease and are more likely to die at a younger age. The detrimental effect of having a low birth weight is exaggerated if rapid growth occurs during the postnatal period and the individual becomes fat. The molecular mechanisms linking poor fetal growth, long-term health and lifespan are not known. Many of our attempts to decipher mechanisms of human diseases both rely on and have benefited from studying animal models. We have shown that in a mouse model that if pregnant animals have too little protein during pregnancy their babies are small at birth. These animals growth very quickly during the lactation period if suckled by a normally fed mother and reach an apparently normal weight by weaning. However these patterns of growth have detrimental consequences for the animal and we have shown results in over a 25 % reduction in lifespan. We now plan to study these animals further to understand how a modest reduction in protein intake of the mother can have such a large effect on the lifespan of her offspring. We are particularly interested in proteins involved in insulin signalling as it is know that insulin has effects on growth and metabolism in mammals and more recently has been implicated in regulation of lifespan in simple organisms such as fruit flies. Once the underlying mechanisms linking maternal diet to the health and longevity of the offspring are understood, intervention strategies can then be developed to help improve the health of both pregnant women and their offspring.