A Look at the Aging Liver

This paper examines some aspects of aging in the liver, giving a general review in the course of getting to a discussion on immune system changes that occur in aging and their influence on the liver. Note the importance of a buildup of unwanted protein byproducts inside liver cells, something that occurs due to the progressive failure of cellular housekeeping components known as lysosomes. You might recall that researchers reversed aspects of liver aging in mice a few years back by boosting lysosomal activity, so as to counteract some of the usual decline.

Although the human liver is not unscathed by the process of aging, the changes it undergoes are minor compared with other organ systems. It has been ascertained that there are no liver diseases specific to advanced age. However, the clinical course and management of liver diseases in the elderly may differ in several aspects from those of younger adults.

Human and experimental studies suggest that, in comparison with other organs, the liver ages fairly well. Aging is however associated with a variety of morphological changes in the liver, but their underlying mechanisms are still unclear. The liver progressively shrinks by 20-40% during the course of a human life, and there is a concomitant age-related decrease in liver volume. The classic gross appearance of the liver in the elderly is known as "brown atrophy", and the brown is due to an accumulation of highly oxidized insoluble proteins, known as lipofuscin, stored into hepatocytes. These accumulations of highly cross-linked protein are thought to relate to chronic oxidative stress and a failure to degrade damaged and denatured proteins. Increasing evidence suggests that lipofuscin interferes with complex cellular pathways.

One of the most important age-related changes in liver function observed in animal models is a significant decrease in regenerative capacity of the liver, but not in the capacity to restore the organ to its original volume. [It] has also been shown that aging is associated with multiple changes in. Elderly humans secrete less bile acid, have increased biliary cholesterol levels, and show an increased oxidative stress that is mainly attributable to a reduced capacity to eliminate metabolically generated superoxide radicals as efficiently as before. The reduction in hepatic blood flow during aging reduces the metabolism of rapidly cleared drugs. Aging of the liver is also associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins.

Link: http://dx.doi.org/10.1186/1742-4933-10-9