Protection of the Heart Against Ischemia/Reperfusion by Silent Information Regulator 1

Myocardial ischemia followed by ischemia/reperfusion (I/R) induces irreversible damage to cardiac muscle. Medical treatment that effectively prevents I/R injury would alleviate the consequent development of cardiac remodeling and failure. Mechanisms that extend life span often make organisms resistant to stress, and an accumulation of such mechanisms may prevent aging and susceptibility to age-associated diseases. Sirtuins are a group of molecules involved in longevity and stress resistance. Stimulation of silent information regulator 1 (Sirt1), the mammalian ortholog of yeast Sir2 and a member of the sirtuin family, extends the life span of mice fed a high-fat diet and retards aging in the heart. Recent evidence suggests that stimulation of Sirt1 mimics ischemic preconditioning and protects the heart from I/R injury, suggesting an intriguing possibility of using longevity factors to treat cardiac disease. Here, we discuss the cardioprotective effects of Sirt1 and possible underlying mechanisms.