Aging and the Liver: An Update

The issue of whether or not liver function is compromised in the elderly population remains unresolved. Numerous age-related changes in hepatic structure and function have been described, but many of these observations are qualitative, were made under suboptimal experimental conditions, or are simply contradictory. Changes in hepato-cellular structural parameters, e.g., increased hepatocyte size, increase in the number of binucleated cells, altered mitochondria, and endoplasmic reticulum, have been reported. However, quantitative morphological analyses have refuted many of these observations. There are few functional data that correlate with structural changes. Serum and biliary cholesterol appear to rise, predisposing elderly people to increased incidences of coronary disease and gallstones, respectively. The rate of liver regeneration declines in old animals, but the regenerative capacity remains unchanged, perhaps reflecting an age-associated reduction in the response to hepatotrophic factors. This senescent change has important clinical implications with regard to surgical intervention for liver disease, e.g., resection or transplantation. Nevertheless, most outcomes studies suggest that age alone should not be a determining factor in such clinical decisions. Geriatric patients exhibit a decline in the hepatic clearance of certain drugs and a marked increase in the frequency of adverse drug reactions, reflecting an increase in polypharmacy regimens and declines in liver volume and blood flow rather than reduced Phase I metabolism. Although the livers of elderly subjects are characterized by a decline in adaptive responsiveness and reduced reserve capacity, clinical tests suggest that liver function is well-maintained in this age group.