Ischemia/reperfusion (I/R) injury is the central cause of global death in cardiovascular diseases, which is characterized by disorders such as angina, stroke, and peripheral vascular disease, finally causing severe debilitating diseases and death. The increased rates of morbidity and mortality caused by I/R are parallel with aging. Aging-associated cardiac physiological structural and functional deterioration were found to contribute to abnormal reactive oxygen species (ROS) production during I/R stress. Disturbed redox homeostasis could further trigger the related signaling pathways that lead to cardiac irreversible damages with mitochondria dysfunction and cell death. It is notable that sirtuin proteins are impaired in aged hearts and are critical to maintaining redox homeostasis via regulating substrate metabolism and inflammation and thus preserving cardiac function under stress. This review discussed the cellular and functional alterations upon I/R especially in aging hearts. We propose that mitochondria are the primary source of reactive oxygen species (ROS) that contribute to I/R injury in aged hearts. Then, we highlight the cardiomyocyte protection of the age-related proteins Sirtuin1 (SIRT1) and Sirtuin1 (SIRT3) in response to I/R injury, and we discuss their modulation of cardiac metabolism and the inflammatory reaction that is involved in ROS formation.
Keywords: ROS; SIRT1; SIRT3; aging heart; ischemia and reperfusion.