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Published on: March 20, 2018
Multi-target synergistic anti-aging: QG extends Caenorhabditis elegans lifespan through DAF-16/FOXO pathways,
Jiahui Wang1, Shuqi Li1, Zichen Lei1
1College of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
Abstract:
Aging not only significantly reduces the quality of life for the elderly but also poses multifaceted challenges to society. Its progression involves the synergistic interaction of multidimensional, multipathway molecular mechanisms, including mitochondrial dysfunction, oxidative stress accumulation, chronic inflammation, and genomic damage. Quercetagetin (QG), as a natural flavanol monomer, exhibits significant potential in anti-aging due to its simultaneous targeting of key aging pathways such as oxidative stress and chronic inflammation. We first evaluated QG's safety profile, finding that 0.02 mg/ml QG did not adversely affect motility, feeding, growth, and reproductive capacity in Caenorhabditis elegans (C. elegans). At this concentration, in vivo experiments using wild-type C. elegans confirmed QG's ability to extend lifespan and enhance oxidative stress resistance. The antioxidant and anti-aging effects of QG were further validated using the daf-16 mutant C. elegans DR26. Subsequently, observation of QG's impact on C. elegans mitochondrial morphology revealed significant reductions in area/perimeter and mitochondria coverage ratio following treatment. This indicates that QG treatment shifts the mitochondrial network from fusion toward fission and reduces overall mitochondrial content. QG can also improve age-related dopaminergic, 5-hydroxytryptaminergic and cholinergic neuron degeneration. Mass spectrometry metabolome analysis revealed that QG significantly affected citrate cycle and glycerophospholipid metabolism. Collectively, QG extends C. elegans lifespan by regulating redox homeostasis, DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming. This multi-target regulatory capacity positions QG as an ideal candidate molecule for anti-aging drug development.
Insights
Quercetagetin (QG) is a natural compound that extends lifespan and enhances stress resistance in C. elegans. It targets multiple aging pathways, including oxidative stress and mitochondrial function, making it a promising anti-aging drug candidate.
Area of Science:
- Gerontology and Molecular Biology
- Natural Product Chemistry
Background:
- Aging is a complex process involving molecular damage, oxidative stress, and inflammation.
- Natural compounds offer potential therapeutic strategies for mitigating age-related decline.
Purpose of the Study:
- To investigate the anti-aging effects and safety of Quercetagetin (QG) in Caenorhabditis elegans (C. elegans).
- To elucidate the molecular mechanisms underlying QG's anti-aging properties.
Main Methods:
- Safety assessment of QG in C. elegans (motility, feeding, reproduction).
- Lifespan extension and oxidative stress resistance assays in wild-type and daf-16 mutant C. elegans.
- Mitochondrial morphology analysis using microscopy.
- Metabolome analysis via mass spectrometry.
Main Results:
- QG (0.02 mg/ml) demonstrated safety in C. elegans.
- QG significantly extended lifespan and enhanced oxidative stress resistance.
- QG treatment altered mitochondrial dynamics, favoring fission and reducing overall content.
- QG improved age-related neurodegeneration and modulated citrate cycle and glycerophospholipid metabolism.
Conclusions:
- QG exhibits multi-target anti-aging effects by regulating redox homeostasis, DAF-16/FOXO pathways, mitochondrial function, and metabolism.
- QG is a promising candidate for anti-aging drug development due to its broad-spectrum activity.
