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See related article, pp 1056–1063 Aging is a powerful determinant of vascular changes, being associated with elastin degradation and accumulation of collagen fibers within the vascular wall, ultimately leading to increased arterial stiffness. The ability of arterial stiffness of predicting cardiovascular events and the availability of techniques that enable its simple measures makes this parameter one of the most utilized in cardiovascular research.1 Exposure to cardiovascular risk factors, including hypertension, smoking, or diabetes mellitus, can amplify and accelerate the vascular remodeling observed with aging, leading to a faster increase of arterial stiffness (a phenomenon known as early vascular aging).2 This is commonly preceded and accompanied by the development of endothelial dysfunction—the earliest manifestation of an altered vascular homeostasis. In a quiescent state, endothelial cells have a key role in regulating the vascular tone and structure. When exposed to cardiovascular risk factors, the endothelium results in a switch in signaling from an NO-mediated silencing of cellular processes toward activation by redox signaling. The overproduction of reactive oxygen species (ROS) reduces NO availability and activates pathways that lead to early vascular remodeling.3 Various enzymatic and nonenzymatic sources of ROS have been identified within the arterial wall of patients with increased vascular stiffness, including nicotinamide adenine dinucleotide phosphate oxidase, cyclooxygenase, xanthine oxidase, and the endothelial NO synthase.3 Among these, mitochondria have recently drawn increasing attention because of their capacity to produce high levels of ROS (mtROS) even under physiological conditions. mtROS is generated at complex I and complex III in …