| Abstract |
Cellular aging causes declining cell functionality, gradually disrupting cellular homeostasis. Mitochondria are crucial in numerous metabolic processes, including the electron transport chain and fatty acid β-oxidation. Mitochondrial dysfunction is closely linked to aging-related liver dysfunction because it impairs fatty acid metabolism, potentially leading to nonalcoholic fatty liver disease. We demonstrated that neferine-induced autophagy suppressed the aging phenotype in proliferative and replicative aging-induced cells and aging liver tissue by reactivating mitochondrial function. Pharmacological analyses revealed that neferine-induced autophagy via the death-associated protein kinase 1 (DAPK1) and c-Jun N-terminal kinase (JNK) signaling pathways despite the lack of AMP activated protein kinase (AMPK) signaling activation. Furthermore, neferine stimulated ATP production and β-oxidation activity in aging cells. Our in vivo experiments demonstrated that oral administration of neferine rejuvenated aging liver tissue, suppressed fatty acid accumulation in the liver, and reduced senescence-associated β-galactosidase activity. Thus, neferine rejuvenated aging cells and liver tissue by inducing autophagy to reactivate mitochondrial function.
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