Study Reveals How Aging Affects Liver Function Through Cell Enlargement and Inflammation

As we age, the liver undergoes significant changes that can impair its vital functions, such as filtering blood, metabolizing nutrients, and detoxifying the body. A recent study conducted by researchers at Weill Cornell Medicine sheds light on the cellular and molecular transformations that contribute to the decline in liver health with age.

Published in the journal Hepatology, the study compares the livers of young and aged mice, alongside human liver samples, to understand how age impacts liver structure and function. The findings reveal that aging livers exhibit enlarged hepatocytes—the primary liver cells—and increased deposits of lipofuscin, a substance associated with cellular aging and damage. These cellular alterations are accompanied by inflammation and a blurring of the liver’s normal zonation, which is crucial for its metabolic activities.

One of the key advancements in this research is the application of single-nucleus RNA sequencing, a cutting-edge technique that profiles gene activity across various cell types. This approach uncovered that aging disrupts the functional organization of hepatocytes, leading to a loss of their specialized zones. Furthermore, the study identified that numerous genes involved in inflammation and senescence—the process where cells lose their ability to divide and function properly—are more active in aged livers. These processes, collectively called "inflammaging," are believed to contribute to increased vulnerability to liver diseases.

The implications of these findings suggest that the aging-related structural and molecular changes in the liver might explain why older individuals are more prone to chronic liver conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD). This common condition, affecting roughly 30-40% of the U.S. population, can progress to cirrhosis and liver cancer if left untreated. Despite the liver’s remarkable capacity for regeneration, the molecular underpinnings of age-related decline remain poorly understood, highlighting the need for targeted therapies.

Lead researcher Dr. Robert Schwartz emphasizes the importance of these discoveries, stating, "Understanding how aging alters liver cell function and organization provides a foundation for developing interventions that could restore youthful liver activity and resistance to disease." The study opens new avenues for research aimed at preventing or reversing liver aging, ultimately improving health outcomes for the aging population.

This research also underscores the broader significance of cellular senescence and inflammation in tissue aging, emphasizing the potential for novel treatments that target these processes to maintain organ resilience throughout life.