Aging and Cardiac Ischemia—Mitochondria and Free Radical Considerations

Abstract

SummaryAcute myocardial infarction (MI, heart attack) kills 200,000 people annually in the United States, and the number 1 risk factor for fatal MI is age. The biological phenomenon underlying MI is ischemia-reperfusion (IR) injury, i.e., damage to tissue that occurs during and immediately after an MI. In this chapter, following a brief primer on mitochondrial ROS generation, and the underlying pathologic mechanisms of mitochondrial dysfunction in IR injury, we then break down the effects of aging on MI risk into three parts. First, changes in risk factors for MI with aging, most of which are external to the heart (e.g., atherosclerosis). Second, changes in cardiac mitochondrial function with age. Third, changes in the response of cardiac mitochondria to MI. Last, the role of mitochondria in protecting the heart from ischemia is introduced, and the possibility that increased MI risk with aging originates from a degeneration of protective signaling pathways is raised. We conclude with an outlook on the therapeutic opportunities, both current and developing, for the treatment of increased MI risk, in aged human populations.