Cellular mechanisms of aging and their impact on the aortic/arterial wall

Vascular aging is associated with altered biochemical, mechanical, and structural feature changes of the vascular wall and by a gradual loss of vascular integrity leading to reduced arterial compliance. Vascular aging is associated with increased risk for cardiovascular disease, the leading cause of death worldwide. From a clinical point of view, it can be defined as a gradually developing process characterized by age-related alterations in structural properties of the vascular wall accompanied by decline in endothelial function resulting in loss of arterial elasticity and increased arterial stiffness. In the presence of comorbidities and/or other diseased conditions related to inflammation, the rate of vascular aging significantly increases. Thus, understanding the exact mechanisms mediating these processes is important for modulation of disease states and potential treatment interventions. Experimental models and human studies have identified interconnected hallmark processes driving aging, which include oxidative stress, vascular inflammation, endothelial dysfunction, and calcification, while from the molecular signaling pathways the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and sirtuins is introduced. In this chapter, we discuss detailed roles of the most important cellular and molecular pathways involved in vascular aging, their association with arterial wall stiffening, and their combined impact on the aortic wall structure in comparison with other vascular beds and in the presence of comorbidities.