Understanding the molecular mechanisms by which maternal diet influences longevity

一个人的饮食对一个人在生命的任何阶段的健康都有重要的影响。然而，有证据表明，孕妇的饮食尤其重要，因为它对多年后婴儿成年后的健康有重大的长期影响。怀孕期间营养不良的婴儿往往出生体重低。研究表明，出生体重过轻的人不仅在分娩时存活的可能性较低，而且患各种常见疾病（如糖尿病、高血压和心脏病）的风险也大大增加，而且更有可能在年轻时死亡。出生体重过低的有害影响会被夸大，如果在出生后迅速生长，个体变得肥胖。胎儿生长不良、长期健康和寿命之间的分子机制尚不清楚。我们破译人类疾病机制的许多尝试都依赖于并受益于对动物模型的研究。我们已经在一个老鼠模型中证明，如果怀孕的动物在怀孕期间摄入的蛋白质太少，它们的婴儿出生时就会很小。如果由正常喂养的母亲哺乳，这些动物在哺乳期生长得很快，断奶时体重明显正常。然而，这些生长模式对动物有不利的影响，我们已经证明，结果是寿命减少了25%以上。我们现在计划进一步研究这些动物，以了解母亲蛋白质摄入量的适度减少如何对其后代的寿命产生如此大的影响。我们对参与胰岛素信号传导的蛋白质特别感兴趣，因为众所周知，胰岛素对哺乳动物的生长和代谢有影响，最近还涉及到果蝇等简单生物的寿命调节。一旦了解了母亲饮食与后代健康和寿命之间的潜在机制，就可以制定干预策略，以帮助改善孕妇及其后代的健康。

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.