Aging under Pressure: The Roles of Reactive Oxygen and Nitrogen Species (RONS) Production and Aging Skeletal Muscle in Endothelial Function and Hypertension-From Biological Processes to Potential Interventions

The proportion of adults living with hypertension increases significantly with advancing age. It is therefore important to consider how health and vitality can be maintained by the aging population until end of life. A primary risk factor for the progression of cardiovascular diseases (CVD) is hypertension, so exploring the factors and processes central to this burden of disease is essential for healthy aging. A loss of skeletal muscle quantity and quality is characteristic in normal aging, with a reduction of vasodilatory capacity caused by endothelial dysfunction, and subsequent increase in peripheral resistance and risk for hypertension. Reactive Oxygen and Nitrogen Species (RONS) encompass the reactive derivatives of NO and superoxide, which are continuously generated in contracting skeletal muscle and are essential mediators for cellular metabolism. They act together as intra and intercellular messengers, gene expression regulators, and induce programmed cell death. In excessive amounts RONS can inflict damage to endothelial and skeletal muscle cells, alter signaling pathways or prematurely promote stress responses and potentially speed up the aging process. The age-related increase in RONS by skeletal muscle and endothelial mitochondria leads to impaired production of NO, resulting in vascular changes and endothelial dysfunction. Changes in vascular morphology is an early occurrence in the etiology of CVDs and, while this is also a normal characteristic of aging, whether it is a cause or a consequence of aging in hypertension remains unclear. This review serves to focus on the roles and mechanisms of biological processes central to hypertension and CVD, with a specific focus on the effects of aging muscle and RONS production, as well as the influence of established and more novel interventions to mediate the increasing risk for hypertension and CVD and improve health outcomes as we age.