While the liver is resilient, stress and aging can impact its health, leading to diseases and potential failure. Researchers have discovered a potential way to reverse liver damage by studying mice and human liver tissue. They found that aging causes certain liver cells to die off, and through experimental drug intervention, they were able to reverse this process.
The study, published in the journal Nature Aging, offers hope for individuals with liver damage caused by factors like high cholesterol, obesity, and diabetes. It shows that aging may be partially reversible, according to lead author Dr. Anna Mae Diehl from Duke University School of Medicine.
The research aimed to understand how non-alcoholic liver disease progresses to cirrhosis, a severe condition leading to organ failure. Aging is a significant risk factor for cirrhosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD), affecting one in three adults globally.
By analyzing mouse livers, the researchers identified genetic differences in old livers, showing increased activation of genes causing liver cell degeneration. This led to the discovery of a specific type of cell death called ferroptosis, dependent on iron and exacerbated by metabolic stressors.
Further analysis of human liver tissue from individuals with MASLD revealed a similar genetic signature, with key genes promoting cell death through ferroptosis being highly activated. By targeting this pathway, researchers were able to reverse liver damage in mice, even in old animals fed disease-inducing diets.
The study’s findings suggest that blocking ferroptosis could help restore liver health, offering hope for individuals with liver diseases like MASLD. By reducing ferroptotic stress, it may be possible to reverse liver damage caused by aging and metabolic stresses.
The research team’s work also highlights the impact of liver damage on other organs, showing that damaged livers can amplify stress in other tissues. By understanding and targeting these mechanisms, researchers aim to develop new treatments for liver diseases and related conditions.
The study was supported by funding from the AASLD Pinnacle Award, the National Institutes of Health, and Boehringer Ingelheim Pharmaceuticals, Inc. Study authors include Kuo Du, Liuyang Wang, Ji Hye Jun, Rajesh K. Dutta, Raquel Maeso-DÃaz, Seh Hoon Oh, and Dennis C. Ko.
