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Early life interventions metformin and trodusquemine metabolically reprogram the developing mouse liver through
Sarah A Ashiqueali1, Augusto Schneider2, Xiang Zhu1
1Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USA.
Aging Cell
|May 27, 2024
Summary
Early life interventions with metformin and trodusquemine reprogram liver metabolism. These compounds induce epigenetic changes, potentially delaying age-related diseases and enhancing longevity.
Area of Science:
- * Developmental Biology
- * Pharmacology
- * Molecular Biology
Background:
- * Early life interventions show potential for enhancing longevity and health.
- * Metformin (MF) exhibits anti-aging properties and delays puberty.
- * Trodusquemine (MSI-1436) combats obesity and metabolic disorders by inhibiting Ptp1b.
Purpose of the Study:
- * To investigate the effects of MF and MSI-1436 on liver metabolic processes in young mice.
- * To uncover biomolecular signatures central to liver metabolism.
- * To explore potential epigenetic reprogramming of the liver transcriptome.
Main Methods:
- * Administration of MF and MSI-1436 to developing mice.
- * Analysis of liver mRNA and miRNA expression.
- * Bioinformatic analysis of differentially expressed miRNAs and their targets.
Main Results:
- * MSI-1436 demonstrated more potent alterations in liver mRNA and miRNA expression than MF.
- * Bioinformatic analysis indicated inhibition of the Pi3k/Akt/Mtor pathway by differentially expressed miRNAs.
- * These pathways regulate de novo lipogenesis, fatty acid oxidation, VLDL transport, and cholesterol metabolism.
Conclusions:
- * Postnatal administration of MF and MSI-1436 metabolically reprograms the liver.
- * These interventions induce epigenetic changes in the transcriptome.
- * This reprogramming may forestall age-related diseases and enhance longevity.
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