Vascular aging.

Despite significant decreases in prevalence over the last 3 decades, cardiovascular diseases (CVD) remain the leading causes of morbidity and mortality in developed nations like the United States. By far, the strongest independent risk factor for CVD is age, with 90% of all CVD occurring in adults age 40 and older (1). Current population projections of a doubling of the number of older adults over the coming decades suggest the possibility of a marked increase in clinical CVD without effective intervention (3). Successful intervention efforts typically are aided by the identification of therapeutic targets, which may attenuate or ameliorate age-related increases in our risk of CVD. Direct effects of aging on the heart certainly contribute, but much of the increased risk can be attributed to changes to the arterial system, termed vascular or arterial aging (5). The latter changes include stiffening of the large elastic arteries, reduced nitric oxide bioavailability associated endothelial dysfunction, impaired regulation of blood flow in response to increased metabolic demand, altered angiogenesis, and structural changes. Accumulating evidence indicates that vascular aging not only increases the risk of CVD (hypertension, coronary and peripheral artery disease, stroke), but plays a major role in the etiology of numerous other common clinical disorders of advancing age including chronic kidney disease, normal cognitive aging and dementia (Alzheimer’s disease), metabolic disease, and reduced exercise capacity, a strong predictor of mortality (6, 11, 12) (Fig. 1). To address these important issues in vascular aging, a workshop was convened at the annual Gerontological Society of American meetings in November 2016 featuring six keynote presentations. In this Journal of Applied Physiology highlighted series on vascular aging, we have updated and translated these presentations into a cornerstone set of brief review articles, while adding new original research articles within this theme. Three of the review articles emphasize the use of preclinical models to advance our understanding of the arterial system with aging. Lee Murfee and colleagues (4) discuss angiogenesis during aging, emphasizing novel cell changes and new ex vivo models to study these properties in microvascular networks. Steve Segal and colleague (10) discuss the molecular and cellular mechanisms operating at the level of the microvasculature that limit skeletal muscle blood flow with aging in mice via impaired ascending vasodilation. Lisa Lesniewski and colleagues (2) discuss how preclinical models can be used to establish proof-of-concept evidence for novel interventions to reverse vascular aging, including pharmacological caloric restriction mimetics that target dysregulated cellular energy sensing pathways in arteries. The other three cornerstone review articles in this series will address clinical research-based approaches to advancing our understanding of vascular aging. Gary Mitchell (7) discusses the pathophysiology and broad clinical impact of aortic stiffening and consequent increases in pressure and flow pulsatility in age-associated CVD, brain aging, and chronic kidney disease. Kerrie Moreau (8) discusses the important role of changes in gonadal function and hormones in vascular aging during the menopausal transition in women. Finally, Doug Seals and colleagues (9) provide an update on healthy lifestyleAddress for reprint requests and other correspondence: D. R. Seals, University of Colorado Boulder, 354 UCB, Boulder, CO 80309 (e-mail: seals @colorado.edu).