The raised blood pressure of age-related hypertension is an interesting problem because (a) it causes a great deal of downstream harm in the form of pressure damage to tissues and associated dysfunctions, (b) the mechanisms controlling blood pressure are actually quite well understood, and so © there are many different ways to reduce blood pressure without actually addressing the underlying cell and tissue damage that causes aging. Studies suggest that control of hypertension via present pharmaceutical approaches can sizeably reduce the risk of age-related disease.
Broadly speaking, blood pressure is determined by the combination of heart rate, constriction of blood vessels throughout the body, and regulation of water content of blood by the kidneys. Complex feedback loops of pressure sensing, blood sodium sensing, and downstream signaling juggle these processes to maintain blood pressure at a given level. Pharmaceuticals are used to block or upregulate portions of that signaling in order to induce reduced blood volume via greater uptake of water by the kidneys or lesser degrees of vessel constriction in order to expand the volume of the vascular system. Heart rate is not typically targeted in this context, for all of the obvious reasons.
In today's open access paper, researchers note that the use of calorie restriction as an intervention acts to reduce the increase of blood pressure in aged rats. It functions via the renin-angiotensin system of the kidney, a part of the regulatory systems that control the water content of blood and thus blood volume. Calorie restriction prevents some of the age-related disruption of this regulatory system, and thus removes some fraction of age-related hypertension.
Aging is associated with imbalances in hormonal and metabolic processes that contribute to homeostasis and enable the organism to adapt to changes in its environment. One of the key control systems that changes during the aging process is the renin-angiotensin system (RAS), which is a critical control system that affects the regulation of blood pressure and sodium balance. During aging, RAS through over activation of AngII/Ang II type 1 receptor and overproduction of reactive oxygen species (ROS) and inflammatory responses acts as an accelerator in cell and organ senescence, and causes to hypertension, chronic kidney disease, atherosclerosis, and sarcopenia. On the other hand, the other parts of RAS, AngII/Ang II type 2 receptor and ACE2 (angiotensin converting enzyme 2)/ Ang (1-7)/Mas receptor, modulate the harmful effect of ACE/Ang II/AT1 receptor and play a positive impact in RAS balance and delay senescence. It seems that both local (tissue) and circulating RAS are involved in aging-related disease.
Several studies suggest the anti-aging effects of ACE-inhibitors and angiotensin receptor blockers (ARBs) in rodent models. Beneficial effects of RAS blockers on aging through increased klotho and sirtuin expression and activation of vitamin D signaling parallel the effects of calorie restriction (CR) in delaying aging. Evidence shows that fasting has a beneficial role on human health by improving various metabolic markers. Our recent findings revealed that the restoration of RAS equilibrium in both the aorta and heart may be a part of involving mechanisms of fasting benefits on its cardiovascular rejuvenation.
In this study, age-related changes in kidney RAS components were evaluated. Then, the effect of a 3-month period of two fasting regimes, fasting one day per week (FW) or fasting every other day (EOD) on the components of renal RAS and arterial blood pressure in three age groups of rats was investigated. The results showed that changes in the blood pressure and kidney-RAS system were not significant until middle age. However, senescence was correlated with a significant increase in blood pressure, decrease in the amount of AT2R protein of kidney, a significant rise in the AT1R / AT2R proteins ratio of kidney and plasma Ang II level, and a significant decrease in klotho plasma level in older rats contrast to young rats. On the other hand, EOD fasting reversed the aging effect on blood pressure and RAS, so that under EOD the mentioned parameters in old rats reduced to levels of young animals and also the ACE2 protein was significantly higher than young animals.
View the full article at FightAging
