Elucidating emerging signaling pathways driving endothelial dysfunction in cardiovascular aging

The risk for developing cardiovascular diseases dramatically increases in older individuals, and aging vasculature plays a crucial role in determining their morbidity and mortality. Aging disrupts endothelial balance between vasodilators and vasoconstrictors, impairing function and promoting pathological vascular remodeling. In this Review, we discuss the impact of key and emerging molecular pathways that transduce aberrant inflammatory signals (i.e., chronic low-grade inflammation-inflammaging), oxidative stress, and mitochondrial dysfunction in aging vascular compartment. We focus on the interplay between these events, which contribute to generating a vicious cycle driving the progressive alterations in vascular structure and function during cardiovascular aging. We also discuss the primary role of senescent endothelial cells and vascular smooth muscle cells, and the potential link between vascular and myeloid cells, in impairing plaque stability and promoting the progression of atherosclerosis. The aim of this summary is to provide potential novel insights into targeting these processes for therapeutic benefit.