"The number of people over the age of 80 years in the 25 EU member states is currently 18.2 million or 4% of the total population; by 2020, 20% of the EU population will be >65 years old which will place considerable burden upon limited health care resources. 70% of older adults report at least one chronic disease that contributes to a reduction in healthspan or the number of extra years spent in good health. The European Commission is committed to identify rational and evidence based approaches to improve health in old age and as such has identified Ageing research as a priority. The most prevalent conditions that contribute to the ageing phenotype are sarcopaenia, hypertension and cardiovascular disease, central adiposity and type 2 diabetes mellitus and osteoporosis. Here there are remarkable similarities to patients with Cushing s syndrome caused by excessive secretion of glucocortiocoids such as cortisol. PRECORT Prereceptor Cortisol metabolism and human Ageing will test the hypothesis that age-related changes in body composition (central adiposity, reduced bone and muscle mass, skin thinning) and resulting chronic disease (diabetes, osteoporosis, sarcopaenia, hypertension, cardiovascular disease) are caused by excessive glucocorticoids as a result of age-related activation of the pituitary-adrenal axis and/or increased 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1), an enzyme that can generate cortisol locally within fat, bone, muscle and skin. The proposal will complete the full cycle of translational research and will potentially offer a new therapeutic approach through selective 11b-HSD1 inhibitors to modulate the ageing phenotype thereby improving the healthspan of the Ageing EU community."