Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation

The world population is aging, and by 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60. Aging itself is a major cardiovascular risk factor, affecting morbidity and mortality of the aging population. At the same time, aging increases the likelihood of the presence of other risk factors. The aged myocardium is characterized by several structural and functional progressive changes that impair its ability to respond appropriately to stressful conditions. Although some progress to understand the complex mechanisms that underlie these phenotypic changes, the molecular pathways that determine the balance between aging and rejuvenation in the aged myocardium still remain elusive. In this article, we review molecular mechanisms responsible for the phenotypic changes observed with aging in the heart, providing insight into molecular pathways and pharmacological interventions that may rejuvenate the aged myocardium. A better understanding of these pathways is essential for determining their therapeutic potential in humans, improving the possibility that the increase in life expectancy that we are observing will be accompanied by a parallel increase in healthspan.