A steady increase in life expectancy has resulted in an equivalent increase in elderly patients who are more susceptible to diseases than young patients. In a recent study, we found that in both in vitro and in vivo models of ischemia/reperfusion (I/R), a loss of ATG4B is causatively associated with the increased sensitivity of the liver to I/R injury with age. Our work suggests that a restoration or enhancement of autophagy is a novel therapeutic modality to ameliorate liver function after I/R to aged livers.