Dietary Nucleotides Mitigate Age-Related Hepatic Lipid Dysregulation and Fibrosis

The aging process is often accompanied by hepatic metabolic dysregulation and related complications, including lipid accumulation and fibrosis. Nutritional interventions are crucial for maintaining metabolic health. This study explored the effects of exogenous nucleotides (NTs) on liver health in aged SAMP8 mice over 9 months. Results demonstrated dietary NTs effectively improved liver pathology, increased body mass, enhanced antioxidant capacity, reduced lipid accumulation, downregulated lipid synthesis genes, and lowered fibrosis-related markers. Mechanistically, NTs downregulated purine biosynthesis, modulating lipid metabolism-related transcription factors to reduce lipid accumulation. Additionally, NTs enhanced the efficiency of glycolysis and increased ATP synthesis. Thus, NTs exhibited substantial effects in regulating energy metabolism, suppressing lipid synthesis, and combating fibrosis. However, the effects displayed a nonlinear dose-dependent relationship, and the precise impact of NT dosage on health remains challenging. This study advances our understanding of NTs' role in aging and metabolic dysregulation.