Our previous study revealed that Sesn2 expression decreased with age, and that the reduction of Sesn2 protein expression in aged myocardium could cause damage to the Sesn2–AMPK–peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) pathway during ischemia-reperfusion; these changes eventually led to increased myocardial intolerance to ischemia and more serious cardiac insufficiency in aged myocardium [36,37]. Here, SESN2 is linked to heart failure.