Figure 7. Model for the responses against APAP injury in young and aged mice. In young mice, APAP induces hepatocyte necrosis around the CV. Necrotic hepatocytes are eliminated by infiltrated macrophages, which is followed by hepatocyte proliferation. In aged mice, APAP induces hepatocyte apoptosis. Apoptotic hepatocytes are HNF4α-TUNEL+ but somehow retain cellular structures including the plasma membrane even at 24 h after the injury, suggesting they are slowly dying. In addition, macrophages are not efficiently recruited to the damaged tissue containing apoptotic hepatocytes. Consequently, the clearance of nonfunctional hepatocytes is delayed and the subsequent hepatocyte proliferation is suppressed in aged mice.