In a groundbreaking study published in Nature Aging, researchers from Duke Health have unveiled a potential breakthrough in liver regeneration that could revolutionize treatment for millions suffering from liver damage. Despite the liver’s remarkable resilience, chronic stress and aging can lead to diseases like cirrhosis, characterized by severe scarring and organ failure.
Aging triggers death of liver cells
Led by Dr. Anna Mae Diehl, the team discovered a mechanism through which aging triggers the death of liver cells, a process they successfully reversed in animal models using an experimental drug. Their findings offer hope to the vast number of individuals with liver damage attributed to metabolic disorders such as high cholesterol, diabetes, and obesity.
The study investigated the progression of non-alcoholic liver disease to cirrhosis, with a focus on metabolic dysfunction-associated steatotic liver disease (MASLD), which affects a significant portion of adults worldwide. Using mouse models, researchers discovered a specific genetic profile in aged livers that activates genes speeding up hepatocyte degeneration, the liver’s main functional cells.
Dr. Diehl explained that aging triggers a type of iron-dependent cell death known as ferroptosis. Metabolic stressors aggravate this process, leading to increased liver damage with time. Studies on human liver tissue affirmed these results, revealing heightened genetic activation of ferroptosis in obese individuals and those with MASLD, contributing to cell death.
Ferroptic stress in livers affects other organs
Armed with this genetic insight, researchers tested Ferrostatin-1—a drug inhibiting the ferroptosis pathway—on mice fed diets inducing MASLD. Remarkably, mice treated with Ferrostatin-1 exhibited livers resembling those of young, healthy counterparts, regardless of age or disease severity. Dr. Diehl expressed optimism for all patients, comparing their findings to rejuvenating old mice’s livers to resemble those of young, healthy ones.
Moreover, the study revealed insights into how ferroptotic stress in the liver impacts other organs, such as the heart, kidneys, and pancreas, highlighting potential broader implications for treating systemic diseases linked to liver dysfunction.
Dr. Diehl’s research emphasizes targeting ferroptotic stress to reduce aging’s effects on non-alcoholic liver disease, possibly reversing its damage.
