The Frail Renin-Angiotensin System

Over the last few decades, the understanding of the renin-angiotensin system (RAS) has advanced dramatically. RAS is now thought to play a crucial role in physiologic and pathophysiologic mechanisms in almost every organ system and is a key regulator of hypertension, cardiovascular disease, and renal function. Angiotensin II (Ang II) promotes inflammation and the generation of reactive oxygen species and governs onset and progression of vascular senescence, which are all associated with functional and structural changes, contributing to age-related diseases. Although the vast majority of the actions of Ang II, including vascular senescence, are mediated by the Ang II type 1 receptor (AT1R), the identification, characterization, and cloning of the angiotensin type 2 receptor has focused attention on this receptor and to its antagonistic effect on the detrimental effects of AT1R. This review provides an overview of the changes in RAS with aging and age-disease interactions culminating in the development of frailty.