DORIAN · Developmental Origins of Healthy and Unhealthy Ageing: The Role of Maternal Obesity

Europe has the highest proportion of elderly people in the world. Cardiovascular disease (CVD), type 2 diabetes (T2D), sarcopenia and cognitive decline frequently coexist in the same aged individual, sharing common early risk factors and being mutually reinforcing. Obesity is a main health concern in the world. In the EU one-third of women of reproductive age are overweight and 20% are obese, a prevalence predicted to double in the next decade. There is growing evidence that maternal obesity increases the long term risk of CVD, T2D and neurodegenerative morbidity in the offspring. This project will clarify if and to what extent maternal obesity leads to premature and unhealthy ageing, by causing early, i.e. pre-/perinatal metabolic and genetic vulnerability, starting from insulin resistance and glucocorticoid exposure, leading to oxidative-stress, telomere/DNA damage, epigenetic changes, interacting with genetic and environmental variability, resulting in altered gene expression/repair, and ultimately in disease during life and pathological ageing. We will investigate the postulated mechanisms during pregnancy and development, their life long consequences in animal models and in large human cohorts followed from prenatal life until ageing, and the possibility to intervene when the condition is still reversible. Surrogate markers to estimate early risk and monitor progression-regression will be defined. This project will comprehensively address the expected impacts listed in the work programme HEALTH.2011.2.2.2-2 targeting the improvement of health and healthy ageing of a broad/broadening European population. The participation of a research intensive SME and European NGOs guarantees success in biomarker discovery-innovation and in dissemination-public preventive programs. The scientific excellence and complementariness of the partners and the relevance of the target health problem will make a highly significant impact on the European policy and research in this area.