been suggested that the liver's enormous functional reserve, To assess the longevity of the liver, arterialized, orits regenerative capacity, and its abundant, dual blood supply thotopic liver grafts were performed using syngeneic are important factors in its ability to maintain its youthful male BN/BiRij rats. Young (5-month-old) livers were properties as its host becomes senescent. 3 transplanted into 5-month-old recipients (group I, n Γ
The livers of most strains of rats are similar to humans in 27), and old (28-month-old) livers were transplanted into the sense that they are not targets of age-related disease and 5-month-old rats (group II, n Γ
28). Recipient survival they continue to function well in senescent animals. 5 The after transplantation was similar in both groups. The aging and survival characteristics of various strains of rats average age of the livers at the time of death was 16.7
have been defined. 6,7 When rats reach the age of 24 to 28 months in group I and 39.1 months in group II. Four of months, they are considered old 8 and they correspond in age the livers in group II survived for more than 4 years to humans in the sixth to seventh decades of life. Using synge-(48.1 to 52.4 months). Early deaths (less than 1 year) after neic rats, we transplanted old livers into young rats and studtransplantation were most commonly caused by biliary ied their function, histology, and longevity. We postulated obstruction and cholangitis in both groups. Late deaths that the old livers would survive for extended periods after (more than 1 year) after grafting were mainly from heart transplantation because of the innate youthful characterisfailure or tumors. None of the animals died of liver failtics of the liver. ure or liver disease. Weight gain in the rats, total serum protein levels, and alanine transaminase levels after MATERIALS AND METHODS transplantation did not differ significantly between the Male BN/BiRij rats from the National Institute of Aging two groups. There was a trend for the histological fea-(Bethesda, Maryland) were used in the experiments, which were tures of aging of the liver-fibrosis, bile duct proliferaapproved by the Institutional Animal Care Committee, University tion, and pigment deposition-to become more prevaof Western Ontario. Young (5-month-old) recipient rats were randomlent as the livers became very old (mean age, 46 months). ized to receive either young livers from 5-month-old donors (group Nevertheless, typical aging changes, as individual find-I, n Γ
28) or old livers from rats that were 28 months old (group II, ings, were absent in nearly half of the oldest organs. The n Γ
27). alterations in morphology had no apparent effect on the Donors. The donor animals had unrestricted access to food and ability of the livers to sustain the lives of the recipients. water up until surgery. The old donors had the characteristic gross features of aged rats including lethargy, piloerection, and hunched The liver of the BN/BiRij rat was capable of surviving posture. The donors were anesthetized by intraperitoneal injection far beyond the maximum life span of BN/BiRij rats, and of sodium pentobarbital (40 mg/kg), and they were given 5 to 10 rats in general. It did not become diseased in the process. mL of crystalloid intravenously for fluid resuscitation during the (HEPATOLOGY 1997;25:421-425.)
dissection. The liver was skeletonized and a polyethylene tube was inserted into the end of the divided common duct. The hepatic artery was dissected from the celiac trunk ligating the gastroduodenal, gas-
The biological process of aging causes alterations in the tric, and splenic branches. The aorta distal to the celiac origin was structure of organs and tissues that generally result in a mobilized and the liver was perfused in situ with 3 mL of 4ΠC Univer- decline in function and a diminished capacity to meet insity of Wisconsin solution given through the aorta. The liver was creased demands. Not all organs are equally affected, howexcised and an additional 3 to 4 mL of University of Wisconsin solu- ever, and the liver in particular endures aging better than tion was perfused via the portal vein. The grafts were preserved in other vital organs. Although the liver is not exempt from age-University of Wisconsin solution for 25 to 35 minutes and the caudate lobe of each was resected at the end of the preservation period for related morphological changes, its homeostatic functions are histological examination. Immediately before grafting, the livers not seriously impaired in the elderly, and liver function tests were flushed with 3 to 4 mL of Ringer's lactate at 4ΠC. The cold remain normal in senescent individuals. 1,2 Ischemic injury, ischemia time ranged from 40 to 60 minutes.
which so commonly affects the heart, brain, and kidneys of Recipients. The recipient rats were fasted for 12 hours before the aged, is exceptional in the liver because atherosclerosis transplantation. The liver was removed and an orthotopic, arterial- rarely occludes the hepatic artery. The liver is not harmed ized transplantation was performed as previously described. 9 The by chronic hypertension, and life expectancy is not limited suprahepatic caval anastomosis was performed with a running 7-0 by any changes in the liver that are age-induced. 3,4 It has prolene suture, and cuff techniques were used for the infrahepatic caval and portal vein anastomoses. The end of the donor aorta with its celiac axis origin was anastomosed to the side of the recipient infrarenal aorta using a 10-0 nylon running suture. The bile ducts From the Departments of