Endothelial dysfunction, vascular remodelling and pro-inflammatory responses are common features of vascular injury during hypertension and aging. Arterial modifications that are present in hypertensive subjects resemble those observed in aged individuals, suggesting that in hypertension, vessels may undergo premature aging. Increased reactive oxygen species (ROS) production is considered a hallmark of vascular aging, as well as for hypertension. Between the many sources of ROS, NADPH oxidase (Nox) is of interest and a major source of ROS in vascular cells. More specifically, Nox1 levels are increased in hypertension and are regulated by pro-hypertensive agents, such as aldosterone (aldo). Here, we postulated that aldo induces vascular damage through Nox1-ROS-dependent regulation of aging-associated mechanisms, leading to hypertension. Levels of aging associated signalling molecules in arteries from stroke-prone spontaneously hypertensive rats (SHRSP) rats and Nox1 knockout mice infused with aldo (300ug/Kg/day) were studied. Gene expression was assessed by qPCR and protein levels by immunoblotting. Aldo levels were quantified by ELISA. In SHRSP rats, mRNA levels of Nox1 (4 fold), aging-associated inflammatory markers, such as RANTES (5- fold), MCP-1 (6-fold) and IL-6 (2-fold); as well as aldo levels (6-fold), H2AX (marker of aging-associated DNA damage – 1.5-fold) and cell cycle inhibitors, P27 (2-fold) and P21 (4-fold), were increased compared with control rats (WKY), p<0.05. In cultured vascular smooth muscle cells (VSMCs) from WKY and SHRSP rats, basal levels of P66shc activation was increased in cells from SHRSP (2.8-fold, p<0.05). Aldo stimulation increased p66shc phosphorylation in WKY (3.1-fold) and SHRSP (2-fold); an effect that was blocked by ML171 (Nox1 inhibitor). In mice treated with aldo, JNK (pro-inflammatory – 69%) and p66SHC (pro-senescence – 92%) activation were increased in mesenteric arteries (p<0.05); an effect blunted in vessels from Nox1 KO mice. In VSMCs from adult and aged control mice, as well as, from adult Nox-1 transgenic mice (VSMC specific overexpression) basal levels of p66SHC (39%) and OGG-1 (48%), markers of senescence, were increased in VSMCs from aged animals and; aldo effects on p66SHC activation were exacerbated in VSMCs from adult Nox1 transgenic mice. In conclusion, aldo may induce vascular injury through Nox1-p66shc-dependent mechanisms and regulation of pro-aging responses, which may be important to the pathogenesis of hypertension.