Ischemic preconditioning: The role of mitochondria and aging

Aging represents a triple threat for myocardial infarction (MI). Not only does the incidence of MI increase with age, but the heart becomes more susceptible to MI induced damage and protective interventions such as ischemic preconditioning (IPC) become less effective. Therefore, any rational therapeutic strategy must be built around the ability to combat the detrimental effects of ischemia in aged individuals. To accomplish this, we need to develop a better understanding of how ischemic damage, protection, and aging are linked. In this regard, mitochondria have emerged as a common theme. First, mitochondria contribute to cell damage during ischemia–reperfusion (IR) and are central to cell death. Second, the protective signaling pathways activated by IPC converge on mitochondria, and the opening of mitochondrial ion channels alone is sufficient to elicit protection. Finally, mitochondria clearly influence the aging process, and specific defects in mitochondrial activity are associated with age-related functional decline. This review will summarize the effects of aging on myocardial IR injury and discuss relevant and emerging strategies to protect against MI with an emphasis on mitochondrial function.

► Mitochondria contribute to healthy aging.
► Mitochondria are central to ischemic cell damage and death.
► Ischemic preconditioning (IPC) acts via mitochondria to reduce damage.
► The efficacy of IPC diminishes in aged individuals.
► Understanding the mitochondria-IPC-aging axis may help to combat this problem.