Developmental ORIgins of Healthy and Unhealthy AgeiNg: the role of maternal obesity--introduction to DORIAN

Abstract

Europe has the highest proportion of elderly people in the world. Cardiovascular disease, type 2 diabetes, sarcopenia and cognitive decline frequently coexist in the same aged individual, sharing common early risk factors and being mutually reinforcing. Among conditions which may contribute to establish early risk factors, this review focuses on maternal obesity, since the epidemic of obesity involves an ever growing number of women of reproductive age and children, calling for appropriate studies to understand the consequences of maternal obesity on the offspring's health and for developing effective measures and policies to improve people's health before their conception and birth. Though the current knowledge suggests that the long-term impact of maternal obesity on the offspring's health may be substantial, the outcomes of maternal obesity over the lifespan have not been quantified, and the molecular changes induced by maternal obesity remain poorly characterized. We hypothesize that maternal insulin resistance and reduced placental glucocorticoid catabolism, leading to oxidative stress, may damage the DNA, either in its structure (telomere shortening) or in its function (via epigenetic changes), resulting in altered gene expression/repair, disease during life, and pathological ageing. This review illustrates the background to the EU-FP7-HEALTH-DORIAN project.

Fig. 1

The hypothesis illustrated in this figure emphasizes the early mutual interaction between co-existing mechanisms that has to be tackled for a full understanding of the long-term consequences of maternal obesity. Specifically, IR, glucocorticoid overexposure, and OS may be involved in the modulation of TL, DNA methylation as well as DNA oxidative and mitochondrial damage as markers and mediators of the premature ageing caused by maternal obesity, leading to chronic disease and unhealthy ageing. This figure is public at www.dorian-fp7.eu (in the project flyer).

Fig. 2

DORIAN integrates human clinical projects with research focussing upon basic mechanisms. It comprises four research work packages (WPs). There are two additional WPs: WP5 is dedicated to dissemination and WP6 to management. This figure is public at www.dorian-fp7.eu.