Ischemic preconditioning in the aging heart: from bench to bedside

Coronary artery disease is the leading cause of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. Cardiac ischemic preconditioning represents the most powerful endogenous protective mechanism against ischemia. Brief episodes of ischemia are able to protect the heart against a following more prolonged ischemic period. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators release and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Opposite studies are questionable for the experimental model used, the timing of ischemic preconditioning, and the selection of elderly patients. Several pharmacological stimuli failed to mimic ischemic preconditioning in the aging heart but exercise training and caloric restriction separately, and more powerfully taken together, are able to completely preserve and/or restore the age-related reduction of ischemic preconditioning.