Study Reveals Genetic Link to Liver Disease in Aging

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The age-related genes cause an iron-dependent type of cell death called ferroptosis.The main focus of the study is nonalcoholic fatty liver disease (NAFLD), also known as “metabolic dysfunction-associated steatotic liver disease (MASLD)”. It causes cirrhosis, or scarring, of the liver’s main cells, hepatocytes, and can lead eventually to organ failure. 

After identifying a cluster of genes that affect the aging of cells in mice, the researchers examined cells collected from humans who had obesity and NAFLD/ MASLD. They found the same genetic signature, suggesting a target for pharmacological therapy. 

To confirm their hypothesis, the researchers caused a group of 3-month-old young mice, and one of 2-year-old mice to develop NAFLD/ MASLD via diet.Some of the older mice also received Ferrostatin-1 injections while continuing to be fed the NAFLD/ MASLD-inducing diet. This was so that the researchers could test the potential therapeutic effects of the drug on aging livers. 

The authors of the new study hope that their findings will lead to therapies for NAFLD/ MASLD. They also found that “these genes are similarly upregulated in a variety of human tissues afflicted by disease and aging, including the liver, heart, kidneys, and the pancreatic tissue affected by diabetes. 

Aslam is an assistant research scientist in the Department of Pathology at the University of Michigan, Ann Arbor, and was not involved in the current study.This points to the possibility of a shared molecular basis for aging-related tissue degeneration across multiple organ systems. Researchers have shown that aging exacerbates nonalcoholic liver disease by creating ferroptic stress, and by reducing this impact, we can reverse the damage. 

 Researchers pointed out that research suggests the molecular underpinnings of ferroptosis have three major aspects: iron metabolism, lipid metabolism, and the antioxidant defense system. These pathways offer a variety of potential targets for therapeutic intervention. 

Hepatocytes, the principal epithelial or parenchymal cells of the liver, account for approximately 80% of the liver’s mass and 70% of its cellular components. They play an indispensable role in metabolism, detoxification, and protein synthesis. The remaining liver structure consists of nonparenchymal cells, including endothelial cells, stellate cells, Kupffer cells, and lymphocytes. Children with [NAFLD/ MASLD] may experience symptoms such as abdominal pain, typically centered in or on the upper right part of the abdomen, and fatigue. However, these may be the result of other issues unrelated to the condition. 

Physical examinations of children might reveal slight liver enlargement and some children and young adults could have patchy, dark skin discoloration (acanthosis nigricans), usually around the neck and underarms. 

NAFLD/ MASLD may be diagnosed in a blood test that shows abnormally high levels of liver enzymes. Blood tests, however, often fail to pick up the condition’s presence. 

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