title: The garlic constituent diallyl trisulfide increases the lifespan of C. elegans via skn-1 activation.
abstract: Medicinal benefits of Allium vegetables, such as garlic, have been noted throughout recorded history, including protection against cancer and cardiovascular disease. We now demonstrate that garlic constituent diallyl trisulfide (DATS) increases longevity of Caenorhabditis elegans by affecting the skn-1 pathway. Treatment of worms with 5-10 μM DATS increased worm mean lifespan even when treatment is started during young adulthood. To explore the mechanisms involved in the DATS-mediated increase in longevity, we treated daf-2, daf-16, and eat-2 mutants and found that DATS increased the lifespan of daf-2 and daf-16 mutants, but not the eat-2 mutants. Microarray experiments demonstrated that a number of genes regulated by oxidative stress and the skn-1 transcription factor were also changed by DATS treatment. Consistently, DATS treatment leads to the induction of the skn-1 target gene gst-4, and this induction was dependent on skn-1. We also found that the effects of DATS on worm lifespan depend on skn-1 activity in both in the intestine and ASI neurons. Together our data suggest that DATS is able to increase worm lifespan by enhancing the function of the pro-longevity transcription factor skn-1.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Powolny
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.forename: Alan
authors.initials: A
authors.lastname: Hubbard
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Fisher
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D005737:Garlic; D007413:Intestinal Mucosa / Q000378:metabolism; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D046228:Microarray Analysis; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000498:Allyl Compounds; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D010936:Plant Extracts; D013440:Sulfides; D014157:Transcription Factors; C042577:diallyl trisulfide; C073702:skn-1 protein, C elegans