The aging liver and the effects of long term caloric restriction

Abstract

The liver undergoes changes in structure and function in old age. There are age-related changes in liver mass, blood flow and hepatocyte and sinusoidal cell morphology. These changes are associated with significant impairment of many hepatic metabolic and detoxification activities. This has implications for systemic aging and age-related disease. For example the age-related impairment of the hepatic metabolism of lipoproteins predisposes to cardiovascular disease. The effects of caloric restriction in the liver are beneficial in terms of ameliorating many of deleterious phenotypic effects of ageing, but from the mechanistic point of view, caloric restriction does not just simply reverse or delay age-related cellular changes. Instead caloric restriction appears to act via discrete cellular mechanisms such as sirtuin pathways that impact cellular bioenergetics, apoptosis and other cellular functions. The liver has as a pivotal coordinating role when dietary intake is reduced, therefore many of the effects of caloric restriction are mediated by the liver.