Aging exacerbates oxidative stress and liver fibrosis in an animal model of Down Syndrome

A new research paper titled “Aging exacerbates oxidative stress and liver fibrosis in an animal model of Down Syndrome” has been published in Aging.

Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer’s disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals.

In this new study, researchers Sebastiano Giallongo, Jessica Ferrigno, Rosario Caltabiano, Giuseppe Broggi, Amer M. Alanazi, Alfio Distefano, Emanuela Tropea, Antonella Tramutola, Marzia Perluigi, Giovanni Li Volti, Eugenio Barone, and Ignazio Alberto Barbagallo from the University of Catania, King Saud University, and Sapienza University of Rome investigated the impact of aging on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice).

“Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation,” the researchers state.

DS liver exhibited an altered inflammatory response and mitochondrial fitness, as the researchers showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displayed dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. These changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation.

Consistently, histological analysis of DS liver revealed increased fibrosis and steatosis, as shown by increased Colo1a11 expression, indicative of potential progression to liver cirrhosis. Therefore, their findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients.

“These results shed a light on the liver’s role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals,” the team concludes.

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