Angiotensin II Increases Oxidative Stress in Aging
Researchers here suggest that angiotensin II expression is maladaptive in the context of aging, provoking greater oxidative stress and harmful downstream consequences for cell and tissue function. If looking to produce therapies based on interfering in angiotensin II receptor signaling, an approach already well established in the treatment of hypertension, the question is always the tradeoff between loss of function and avoidance of damage. Few if any molecular interactions in the body are entirely dispensable, and angiotensin II signaling is involved in a range of normal cellular processes. That said, this topic is well explored via the existing uses of angiotensin II receptor blockers.
For the last few decades, the involvement of the renin-angiotensin system (RAS) in mediating vasoconstriction, ion entry and excretion, fibrosis, inflammatory and oxidative stress has been well documented. In addition to the circulating system, elements of the RAS are also found in diverse tissues of the brain, heart, and kidney, and contribute to the aging of these organs. Within the brain, different components of the RAS have been extensively studied in the context of neuroprotection and cognition. Alterations in the brain RAS during aging may establish a link between impairment of autonomic reflex function and metabolic changes in aging. Further evidence for the relevance of the RAS in aging is derived from numerous experiments in vivo and in vitro, indicating that aging is accompanied by the increased activity of angiotensin II (Ang II), which is the major bioactive peptide of this system.
A prospective observational study effectively proved that the lifespan of mice with disrupted Ang II type 1 receptor (AT1R) was remarkably longer than that in the control group and showed that the mice lacking AT1R exhibited less oxidative damage, consequently indicating that Ang II-induced reactive oxygen species (ROS) by AT1R seemed to play a crucial part in the aging process. Considering that mitochondria are a key source of endogenous ROS and telomeres are particularly vulnerable to oxidative stress, in this article, we first describe the diverse components of the RAS as well as their physiological functions coupling with each other. Then, we provide an overview of the primary ROS sources and the mechanistic association of ROS with mitochondria and telomeres. This is followed by the discussion of the seemingly universal roles of mitochondrial dysfunction and telomere attrition in aging and how Ang II influences them, conducing to present new preventive strategies in fighting aging and age-associated diseases.