Programming of ageing and age-related diseases
Human epidemiological and animal studies indicate that in addition to life style and genetic factors, environmental influences in prenatal life have a major impact on brain ageing and age-associated brain disorders.
The first indication that ageing may already start in the womb came from a study performed almost 20 years ago in Hertfordshire which showed that people born small lived shorter lives than people who were born larger. Studies in numerous populations worldwide have since shown that a small size at birth, which serves as a proxy of the suboptimal early life experiences is associated with increased risks of chronic degenerative diseases such as type 2 diabetes, cardiovascular disease, several forms of cancer, chronic obstructive airways disease, osteoporosis and sarcopenia. It was hypothesized that adaptations made by the fetus in response to undernutrition result in permanent changes in physiology and metabolism that later induce chronic degenerative disease. The first direct evidence for this hypothesis in humans has come from the studies by Roseboom’s group showing that prenatal exposure to the Dutch famine may lead to an increased risk for type 2 diabetes, cardiovascular disease, breast cancer, renal and lung diseases.
It is well established now that epigenetic modifications during the fetal period induced by maternal stress, therapies with stress hormones (glucocorticoids) or nutrient restriction have a significant impact on health for the entire duration of an individual’s life. Analysis of this link is the key to identifying preventive and therapeutic procedures. Hence, in the present project, the focus is placed on analyzing the link between human development and brain ageing and age-associated diseases such as cognitive decline and stroke.