title: Ethanol-induced differential gene expression and acetyl-CoA metabolism in a longevity model of the nematode Caenorhabditis elegans.
abstract: Previous studies have shown that exposing adults of the soil-dwelling nematode Caenorhabditis elegans to concentrations of ethanol in the range of 100-400mM results in slowed locomotion, decreased fertility, and reduced longevity. On the contrary, lower concentrations of ethanol (0.86-68mM) have been shown to cause a two- to three-fold increase in the life span of animals in the stress resistant L1 larval stage in the absence of a food source. However, little is known about how gene and protein expression is altered by low concentrations of ethanol and the mechanism for the increased longevity. Therefore, we used biochemical assays and next generation mRNA sequencing to identify genes and biological pathways altered by ethanol. RNA-seq analysis of L1 larvae incubated in the presence of 17mM ethanol resulted in the significant differential expression of 649 genes, 274 of which were downregulated and 375 were upregulated. Many of the genes significantly altered were associated with the conversion of ethanol and triglycerides to acetyl-CoA and glucose, suggesting that ethanol is serving as an energy source in the increased longevity of the L1 larvae as well as a signal for fat utilization. We also asked if L1 larvae could sense ethanol and respond by directed movement. Although we found that L1 larvae can chemotax to benzaldehyde, we observed little or no chemotaxis to ethanol. Understanding how low concentrations of ethanol increase the lifespan of L1 larvae may provide insight into not only the longevity pathways in C. elegans, but also in those of higher organisms.
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA. Electronic address: apatanan@ucla.edu.
authors.forename: Alexander Nikolich
authors.initials: AN
authors.lastname: Patananan
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA. Electronic address: lauren.budenholzer@yale.edu.
authors.forename: Lauren Michelle
authors.initials: LM
authors.lastname: Budenholzer
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. Electronic address: ascia@ucla.edu.
authors.forename: Ascia
authors.initials: A
authors.lastname: Eskin
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA. Electronic address: etorres@chem.ucla.edu.
authors.forename: Eric Rommel
authors.initials: ER
authors.lastname: Torres
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA. Electronic address: clarke@chem.ucla.edu.
authors.forename: Steven Gerard
authors.initials: SG
authors.lastname: Clarke
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008136:Longevity; D017423:Sequence Analysis, RNA
chemical_list: D000431:Ethanol; D000105:Acetyl Coenzyme A
keywords: Aging; Caenorhabditis elegans; Ethanol; Fatty acid metabolism; L1 larvae