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Liver Update: Relationship between aging and liver disease

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eMediNexus    01 October 2020

Aging is not an ailment but is considered as a major risk factor for all the chronic diseases, which account for 60% of all deaths across the world. Aging indicates a multidimensional process of organism degeneration. The liver is a vital organ with varied functions that include protein synthesis, detoxification and production of compounds required for digestion. Specific age-related hepatic changes are reported, including increased hepatocyte size, rise in the number of binucleated cells, and decrease in mitochondrial number, which might significantly affect liver morphology, physiology, and oxidative capacity. In the elderly population, a one-third loss of hepatic volume and perfusion occurs from the ages of 30 - 100 years.

The liver is the only organ that is capable of natural regeneration of lost tissue. Even 25% of liver can regenerate into a whole liver. The aging process increases the likelihood of hepatic functional and structural impairment and also metabolic risk. The most common liver disease, which affects one-third of the overall population, is non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by an intrahepatic accumulation of lipids. NAFLD is considered as the hepatic manifestation of metabolic syndrome, which is a cluster of abnormalities consisting of insulin resistance and increases the susceptibility to type 2 diabetes and cardiovascular disease. Insulin resistance is observed in almost 60% of all patients with NAFLD. Insulin resistance is assumed to be the primary cause of NAFLD.

NAFLD can progress to nonalcoholic steatohepatitis (NASH) in the presence of inflammation and oxidative stress. NASH could be a serious risk factor for fatal liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). NAFLD is reversible in its early stages but its treatment becomes very complicated in the advanced stage. NASH might progress to cirrhosis if not treated early and can possibly result in HCC.

The aging process is influenced by an unbalanced stimulation or response of the immune system, which is characterized by elevated levels of inflammatory markers such as cytokines, reactive oxygen species (ROS), chemokine and decreased levels of antioxidant enzymes that include superoxide dismutase (SOD) and phase 1 detoxifying enzymes (inflamm-aging theory). As per this theory, the persistence of inflammatory stimuli over a period of time characterizes the biological background favouring predisposition to age-related diseases. The occurrence of HCC is significantly decreased in the elderly aged more than 70 years.

Source: Sheedfar F, Di Biase S, Koonen D, Vinciguerra M. Liver diseases and aging: friends or foes? Aging Cell. 2013 Dec; 12(6):950-4. doi: 10.1111/acel.12128. Epub 2013 Jul 30. PMID: 23815295.

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