title: Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf.
abstract: Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging.
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.|Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd, Hiroshima 739-1195, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd, Hiroshima 739-1195, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kodera
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Hirata
authors.affiliation: Joslin Diabetes Center, Harvard Stem Cell Institute, and Harvard Medical School Department of Genetics, Boston, MA 02215, USA.
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizunuma
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D005737:Garlic / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; C086300:S-allylmercaptocysteine; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C073702:skn-1 protein, C elegans; C065299:S-allylcysteine; D003545:Cysteine