Aging of the liver: facts and theories

Although most theories of aging assume that cellular functions decline with aging, many intracellular functions in the liver, such as enzyme activities, stay fairly stable in old age. This does not appear to be an antifact caused by in vitro experimental design, since in vivo pharmacokinetic data also demonstrate that most, if not all, biotransformation capacities of the liver remain stable during the aging process, if we take the decline in liver volume with age into account. Thus, many theories to explain the decline in cellular functions during aging appear to be based on erroneous assumptions. The stability of cellular function in old age does not necessarily mean, however, that all cellular functions are identical for young and old organisms. Once unfavorable conditions, such as malnutrition, infection, etc., are involved, the response of the liver is quite different for young and old subjects, demonstrating a more efficient and versatile response in young animal livers in comparison to old livers. Large differences in enzyme activities between young and old organisms appear during stress and especially during recovery from stress. Accordingly, any aging theory needs to explain a potential difference in liver functions (such as response capability) rather than the difference in basal functions. In contrast to rather stable intracellular functions, the uptake function of the hepatocyte surface membranes was found to be progressively decreased with age. This was shown for at least two different types of carrier systems in the surface membranes. Although the decrease of carrier unit number for these substances remains a possible causal factor, we suggest that the decline in hepatic uptake with age is at least partially the result of a gradual decrease in the mobility of surface membrane proteins, which can be shown by the fluorescence recovery after photobleaching (FRAP) technique. Theories of aging need to be elaborated on the basis of unbiased observations on the actual manifestations of cellular aging.