Neferine Attenuates Aging-Related Liver Dysfunction by Suppressing Cellular Aging via Mitochondrial Reactivation

Area of Science:

• Cellular and Molecular Biology
• Gerontology
• Hepatology

Background:

• Cellular aging impairs functionality and homeostasis, with mitochondrial dysfunction closely linked to liver aging and nonalcoholic fatty liver disease.
• Mitochondria are vital for metabolic processes like the electron transport chain and fatty acid oxidation, crucial for liver health.
• Impaired mitochondrial function in aging contributes to liver dysfunction and fatty liver disease development.

Purpose of the Study:

• To investigate the effects of neferine on cellular aging and mitochondrial function.
• To elucidate the molecular pathways, including autophagy and specific signaling pathways, involved in neferine's anti-aging effects.
• To evaluate neferine's potential to reverse age-related liver dysfunction and improve metabolic parameters.

Main Methods:

• Induction of cellular and liver aging models, followed by treatment with neferine.
• Pharmacological analysis of neferine-induced autophagy via death-associated protein kinase 1 (DAPK1) and c-Jun N-terminal kinase (JNK) signaling pathways.
• Assessment of mitochondrial function, ATP production, β-oxidation, and in vivo liver health markers after neferine administration.

Main Results:

• Neferine induced autophagy, suppressed cellular aging phenotypes, and reactivated mitochondrial function in aging cells and liver tissue.
• Neferine activated autophagy through DAPK1 and JNK signaling, independent of AMPK activation.
• Neferine stimulated ATP production and β-oxidation, reduced liver fatty acid accumulation, and decreased senescence-associated β-galactosidase activity in vivo.

Conclusions:

• Neferine effectively rejuvenates aging cells and liver tissue by enhancing autophagy and restoring mitochondrial function.
• The study highlights neferine as a potential therapeutic agent for age-related liver dysfunction and metabolic disorders.
• Neferine's mechanism involves specific DAPK1/JNK-mediated autophagy induction, offering a novel therapeutic strategy for aging.