Critical role of autophage in ischemia/reperfusion injury to aged livers

Abstract

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.

Figure 1

Scheme of hepatocyte death after I/R in aged livers. Young livers have a robust autophagic responsiveness to mild stress, such as normoxia and starvation, as well as moderate ischemia/reperfusion (I/R). As a consequence of increased mitophagy that can eliminate abnormal or dysfunctional mitochondria in a timely manner, MPT onset and hepatocyte death do not occur in young livers. Despite a strong tolerance against mild stress, aged livers poorly tolerate I/R injury due to impaired autophagy, which in turn promotes the onset of the MPT and cell death.