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Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans
Published on: December 9, 2022
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Modulation of cellular thiol status affects FoxO activity and life span
Nadine Urban1, Dimitrios Tsitsipatis1, Andrea Gille1
1Friedrich-Schiller-Universität Jena (Institute of Nutrition), Department of Nutrigenomics, Germany.
Free Radical Biology & Medicine
|October 14, 2015
Summary
Diethyl maleate (DEM) exposure alters FoxO protein location in cells and roundworms, enhancing stress resistance and extending lifespan in C. elegans by modulating aging processes.
Area of Science:
- Cell Biology
- Genetics
- Gerontology
Background:
- Diethyl maleate (DEM) is a thiol-depleting agent used in cell culture.
- Insulin signaling pathways involve FoxO transcription factors, crucial for cellular regulation.
- FoxO proteins play roles in stress resistance and aging.
Purpose of the Study:
- To investigate DEM's effect on insulin signaling via FoxO transcription factors.
- To determine DEM's impact on cellular stress resistance and organismal lifespan.
- To explore DEM's influence on FoxO subcellular localization.
Main Methods:
- Exposure of HepG2 cells and C. elegans to DEM.
- Overexpression of EGFP-tagged FoxO1a in HepG2 cells.
- Analysis of FoxO DNA binding activity and gene expression.
- Assessment of C. elegans survival under oxidative stress (paraquat).
- Monitoring DAF-16 (C. elegans FoxO ortholog) localization and lifespan.
Main Results:
- DEM induced nuclear accumulation of FoxO1a in HepG2 cells, overriding insulin signaling.
- FoxO-regulated gene expression was downregulated despite increased DNA binding.
- DEM exposure increased C. elegans survival against paraquat-induced oxidative stress.
- Nuclear localization of DAF-16 was observed in DEM-treated C. elegans.
- DEM extended C. elegans lifespan in a concentration-dependent manner.
Conclusions:
- DEM modulates FoxO subcellular localization in both cell cultures and whole organisms.
- DEM pre-exposure confers enhanced resistance to oxidative stress.
- DEM acts as a lifespan-extending agent in C. elegans, decelerating aging.
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