@article{f11f95ba2da942e89383ccfea953fc05,
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.",
keywords = "Aging, C. elegans, Diallyl trisulfide, Garlic, Gst-4, Microarray, Skn-1",
author = "Powolny, {Anna A.} and Singh, {Shivendra V.} and Simon Melov and Alan Hubbard and Fisher, {Alfred L.}",
note = "Funding Information: Caenorhabditis elegans strains TJ1060 (spe-9(hc88); fer-15(b26)) ( Fabian and Johnson, 1995 ), DA1113 (eat-2 (ad1113)) ( Raizen et al., 1995 ), CF1038 (daf-16(mu86)) ( Lin et al., 1997 ), CL2166 (dvIs19[pAF15(gst-4::GFP::NLS)]) ( Link and Johnson, 2002 ), and TJ356 (zIs356) ( Henderson and Johnson, 2001 ) were provided by the Caenorhabditis Genetics Center (Minneapolis, MN) which is supported by NIH funding. ALF105 (eat-2 (ad1113); dvIs19[pAF15(gst-4::GFP::NLS)]) and GL227 (daf-2 (e1371); spe-9(hc88); fer-15(b26)) were generated by standard crosses. LG333 (skn-1(zu135);Is007[skn-1::gfp]), LG335 (skn-1(zu135)/nT1[qIs51]), LG348 (skn-1(zu135)/nT1[qIs51];geIs9[gpa-4p::skn-1b::gfp]), and LG357 (skn-1(zu135)/nT1[qIs51];geIs10[ges-1p::skn-1c::gfp]) strains were a generous gift from Drs. Nicholas A. Bishop and Leonard Guarente (MIT, Cambridge, MA) ( Bishop and Guarente, 2007 ). CL691 (dvIs19[pAF15(gst-4::GFP::NLS)]; skn-1(zu67) IV/nT1[unc D -?(n754); let-?]) was a generous gift from Dr. Chris Link (U. Colorado, Boulder, CO) ( Rea et al., 2007 ). Funding Information: This work was supported by a pilot project grant from the University of Pittsburgh Cancer and Aging program project grant ( CA103730 ). A.F. was supported by a grant from the NIA ( K08 AG028977 ). S.V.S was supported by a grant from the NCI ( CA113363 ). S.M. was supported in part by funds from a Nathan Shock award from the NIA ( P30AG025708 ).",
year = "2011",
month = jun,
doi = "10.1016/j.exger.2011.01.005",
language = "English (US)",
volume = "46",
pages = "441--452",
journal = "Experimental Gerontology",
issn = "0531-5565",
publisher = "Elsevier Inc.",
number = "6",
}