Biological aging is commonly associated with compromised cardiovascular function. In particular, cardiac aging is featured by unfavorable left ventricular remodeling, loss of compliance, and poor contractile reserve. Among possible contributing factors for cardiovascular aging, dampened autophagy response has received much attention. Recent evidence also noted a decline in ischemia-reperfusion (I/R) response and mitochondrial content in aging. I/R stress is commonly seen in the setting of cardiac surgery representing a clinical dilemma accompanied by possible myocardial injury if not handled correctly. Although overproduction of reactive oxygen species has been indicated to play a role in aging-associated more pronounced I/R injury, little is known for the mechanism of action (in particular the role of autophagy and mitophagy) and possible sequelae of poor I/R stress response in aging.