Recent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases.

The metabolic syndrome (MetS) presents an increasing prevalence in elderly people. A significant role in MetS is played by the stress response and cortisol. The hypothalamic-pituitary-adrenal (HPA) axis activity is increased by central (loss of hippocampal glucocorticoid receptors) and peripheral (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1, hyperactivity) mechanisms. The HPA hyperactivity has been found in chronic diseases affecting the endocrine (abdominal obesity with MetS, type 2 diabetes), cardiovascular (atherosclerosis, essential hypertension), and nervous systems (dementia, depression), in aging. A novel therapeutic approach (11β-HSD1 inhibition) is promising in treating the HPA axis hyperactivity in chronic diseases with MetS. A large-scale national clinical trial (AGICO, AGIng, and COrtisol study) has been proposed by our group to evaluate the role of cortisol and MetS in the main pathologies of aging (vascular and degenerative dementia, cardiovascular diseases, type 2 diabetes, abdominal obesity).