CHANGES IN THE RENIN-ANGIOTENSIN-ALDOSTERONE AXIS IN LATER LIFE

The renin-angiotensin-aldosterone system (RAAS) is one of the main systems involved in the regulation of blood pressure and sodium homeostasis. In animal experiments and in humans, the plasma renin activity and aldosterone levels are reduced with aging. The age-related differences in plasma renin activity and aldosterone are more pronounced in stimulated conditions (when sitting in an upright position, when salt intake is restricted and when plasma volume is depleted) than under basal conditions. Age-related alterations of the kidney (glomerulosclerosis, decreased number of functional nephrons) might account for the age-related differences in the active to inactive plasma renin ratio. In the same way, a diminished synthesis of angiotensinogen by the liver could contribute to the decrease in the activity of the RAAS in aging. This is partially compensated for by increases in the density of angiotensin II receptors reported in elderly patients. Furthermore, aging is associated with a reduced adrenal responsiveness to angiotensin II, contributing to lower production of aldosterone and alterations of sodium homeostasis. Estradiol and progesterone help stimulate the secretion of renin. Reduced levels of these hormones at menopause also lead to reduced plasma renin activity. In relation to these findings, several studies have shown that reductions in blood pressure, induced by short or long term treatment with angiotensin converting enzyme (ACE) inhibitors, were more pronounced in old than young hypertensive patients. An insertion/deletion polymorphism in the ACE gene has been described; the genotype deletion/deletion of this gene has been reported to be closely associated with longevity. This result was unexpected since the same deletion polymorphism was also shown to represent a potent risk factor for myocardial infarction.