Age-related changes in liver structure and function: Implications for disease ?

The geriatric populations of many countries are growing rapidly and they present major problems to healthcare infrastructures from both medical and economic perspectives. The elderly are predisposed to a variety of diseases, which contribute to a marked increase in morbidity in this subpopulation. The incidence of liver disease increases in the elderly, but the cellular and subcellular perturbations that underlie this suspected predisposition to pathology remain unresolved. Several age-related changes have been documented, including (a) a decline in liver volume, (b) an increase in the hepatic dense body compartment (lipofuscin), (c) moderate declines in the Phase I metabolism of certain drugs, (d) shifts in the expression of a variety of proteins and (e) diminished hepatobiliary functions. Other more subtle changes (e.g., muted responses to oxidative stress, reduced expression of growth regulatory genes, diminished rates of DNA repair, telomere shortening) may contribute to reduced hepatic regenerative capacity, shorter post-liver transplant survival and increased susceptibility to certain liver diseases in the elderly.