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Updated: May 17, 2025
10:51
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
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Targeting farnesoid X receptor as aging intervention therapy
Lijun Zhang1, Jing Yu1, Xiaoyan Gao1
1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Acta Pharmaceutica Sinica. B
|May 15, 2025
Summary
The drug obeticholic acid (OCA) may extend lifespan and healthspan by enhancing detoxification pathways. This FXR agonist increased resistance to toxicants and activated detoxification genes in mice and worms.
Area of Science:
- Aging and toxicology research
- Nuclear receptor signaling
- Genetics and longevity
Background:
- Environmental toxicants are linked to aging and age-related diseases.
- Enhanced detoxification gene expression is a marker of longevity in various species.
- Long-lived animals exhibit increased resistance to toxicants.
Purpose of the Study:
- To investigate the potential of farnesoid X receptor (FXR) agonist obeticholic acid (OCA) to extend lifespan and healthspan.
- To determine if OCA enhances detoxification pathways and resistance to toxicants.
- To elucidate the role of FXR in OCA's longevity effects.
Main Methods:
- Treatment of Caenorhabditis elegans and chemical-induced senescent mice with OCA.
- Assessment of lifespan, healthspan, and toxicant resistance.
- Gene expression analysis of detoxification markers.
- Longevity studies in FXR-deficient mice and C. elegans mutants.
- Metabolome analysis in mouse liver.
Main Results:
- OCA extended lifespan and healthspan in C. elegans and mice.
- OCA enhanced resistance to toxicants and activated detoxification genes in both models.
- Longevity effects of OCA were reduced in FXR-deficient or homologous mutant organisms.
- OCA increased endogenous pregnane X receptor (PXR) agonist levels in mouse liver.
Conclusions:
- OCA shows potential for extending lifespan and healthspan.
- FXR activation by OCA promotes longevity through enhanced detoxification.
- Targeting FXR may be a viable strategy for promoting longevity and healthspan.
Keywords:
AgingDetoxificationFarnesoid X receptorHealthspanLifespanLongevityObeticholic acidPregnane X receptorMore Related Videos
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