Cardiovascular disease (CVD) is the leading cause of the death worldwide and its prevalence greatly increases with advancing age. Vascular aging and hypertension (HTN) are independent risk factors for CVD. We have previously shown that mice with inducible smooth muscle cell-specific deletion of mineralocorticoid receptor (SMC-MR-KO) lack the aging-associated rise in blood pressure (BP) that occurs in MR-intact littermates, confirming a new role for SMC-MR in aging-associated HTN. Here, we sought to characterize changes in vascular and cardiac fibrosis with aging and to explore the role of SMC-MR in the molecular regulation of aging-associated HTN. All mice were anaesthetized under isoflurane for tissue harvests and ex vivo studies. Histological analyses of aortas, carotids, renal arterioles and left ventricles reveal that vascular and cardiac fibrosis increase with aging and are attenuated in SMC-MR-KO mice (p<0.05 vs. MR-intact). Global gene expression profiling reveals a network of fibrosis-related genes that is down-regulated with aging in SMC-MR-KO mice, suggesting a possible mechanism for the reduced vascular fibrosis with aging observed in SMC-MR-KO mice. Next, we hypothesized that SMC-MR contributes to BP regulation with aging by regulating vascular L-type calcium channel (LTCC) expression and/or function. Patch clamp studies on mesenteric resistance vessel SMC from young (3-4 mo.) and aged (9-12 mo.) MR-intact and SMC-MR-KO mice reveal reduced LTCC current density in aged SMC-MR-KO (p<0.05 vs. MR-intact). Fura-2 photometry studies in mesenteric resistance vessels reveal decreased Ca2+ flux in aged SMC-MR-KO (p<0.05 vs. MR-intact) in response to BayK8644 (LTCC agonist). Contraction to BayK8644 is blunted in aged SMC-MR-KO mesenteric resistance vessels (p<0.05 vs. MR-intact). RNA expression of Cav1.2, the pore-forming subunit of LTCC, is reduced by 60% in aged SMC-MR-KO versus MR-intact mice (p<0.05). Micro-RNA expression profiling identified miR-155 as being modulated by SMC-MR with aging. Mesenteric resistance vessel miR-155 expression is increased in aged SMC-MR-KO mice (p<0.05 vs. MR-intact). Ingenuity pathway analysis identified Cav1.2 as a potential target of miR-155. Overexpression of miR-155 in mouse mesenteric SMC reduced Cav1.2 expression by 45% (p<0.05 vs. ctrl). Together, these data suggest that SMC-MR contributes to aging-associated CVD via the regulation of vascular and cardiac fibrosis in addition to the regulation of vascular L-type calcium channels. These results not only enhance our basic understanding of vascular aging and BP control with aging, but also provide support for the identification of innovative therapeutic targets to treat aging-associated HTN and reduce the substantial burden of cardiovascular morbidity and mortality in the aging population.