Mechanisms of Cardiovascular Aging

Abstract

Aging is a major driver of cardiovascular (CV) disease. Incidence of stroke and myocardial infarction increases, and is associated with worsening outcomes, in relation to patient age. Therefore, by studying chronological age in relation to other CV risk factors, pertinent mechanisms of senescence and disease in the heart and blood vessels can be delineated. This is a rather complex process that entails activation of detrimental molecular pathways. An emerging science is revealing intricate signalling cascades which may explain why cardiac and vascular aging are accelerated in the context of CV risk factors. The identification of novel molecular pathways may provide critical insights for mechanism-based therapeutic strategies to prevent premature aging and related CV disease burden. Our lab, as well as other investigators, has recently identified aging and longevity genes and their participation to early vascular and cardiac disease. In the present review, we discuss recent advances in the pathophysiology of age-related vascular and myocardial disease: i) altered nitric oxide signalling as a determinant of vascular and microvascular dysfunction; ii) determinants of mitochondrial oxidative stress; iii) emerging links between oxidant and inflammatory genes; and iv) mechanisms of endothelial and cardiac progenitor cell dysfunction as well as therapeutic implications for vascular and myocardial repair. Such a mechanistic overview illuminates attractive molecular targets for the prevention of age-driven pathology in the vasculature and the heart.