Viewing the reality of aging from the arterial wall beings with the realization that arterial diseases, e.g. atherosclerosis and hypertension, are rampant in Western society and increase exponentially with advancing age. Progressive changes occur throughout life in the structure and function of central arteries in numerous species. These changes include diffuse intimal and medial thickening, and enhanced stiffening. Age-associated remodeling of the aortic wall of both animals and humans involves a proinflammatory profile of arterial cell and matrix properties. This profile features increased production of angiotensin II (Ang II) and downstream Ang II/AT₁ receptor signaling molecules, e.g., matrix metalloproteases (MMPs), calpain-1 and monocyte chemoattractant protein (MCP-1), transforming growth factor â1 (TGF-â1) NFêb, TNFá, iNOS, and VCAM. Activation of calpain-1, MMPs, TGF-â, and NADPH oxidase within the arterial wall is increased, and nitric oxide bioavailability is reduced. Both invasive and proliferative capacities of early passage vascular smooth muscle cells (VSMC) isolated from the aged arterial wall are increased, and are linked to augmented Ang II signaling. This age-associated arterial proinflammatory secretory profile within the grossly appearing arterial wall and related structural/functional remodeling, is reproduced in young rats by chronic infusion of Ang-II.

A megacept emerges with the realization that in arteries of younger animals, in response to experimental induction of hypertension or early atherosclerosis or diabetes, parts of this proinflammatory profile within the arterial wall that have been studied to date are strikingly similar to the profile that occurs with advancing age.

Thus, “aging”-associated arterial changes and those associated with hypertension (and early atherosclerosis and diabetes) are fundamentally intertwined at the cellular and molecular levels. In humans, other well-known risk factors (e.g., excess food intake, altered dietary lipid and metabolism, smoking, and lack of exercise) likely interact with this arterial substrate that has been altered during aging, and that renders the aging artery a “fertile soil” that facilitates the initiation and progression of these arterial diseases. Some lifestyle and pharmacologic interventions have already proved to be effective in preventing or ameliorating hypertension associated with aging. The cellular/molecular proinflammatory mechanisms that underlie arterial aging are novel putative candidates to be targeted by interventions aimed at attenuating arterial aging, and thus attenuating the major risk factor for hypertension.