title: Sesamin extends lifespan through pathways related to dietary restriction in Caenorhabditis elegans.
abstract: OBJECTIVE
  Sesamin, a polyphenolic compound found in sesame seeds, has been reported to exert a variety of beneficial health effects. We have previously reported that sesamin increases the lifespan of Caenorhabditis elegans. In this study, we investigated the molecular mechanisms underlying the longevity effect of sesamin in C. elegans.
  
  
  METHODS
  Starting from three days of age, Caenorhabditis elegans animals were fed a standard diet alone or supplemented with sesamin. A C. elegans genome array was used to perform a comprehensive expression analysis. Genes that showed differential expression were validated using real-time PCR. Mutant or RNAi-treated animals were fed sesamin, and the lifespan was determined to identify the genes involved in the longevity effects of sesamin.
  
  
  RESULTS
  The microarray analysis revealed that endoplasmic reticulum unfolded protein response-related genes, which have been reported to show decreased expression under conditions of SIR-2.1/Sirtuin 1 (SIRT1) overexpression, were downregulated in animals supplemented with sesamin. Sesamin failed to extend the lifespan of sir-2.1 knockdown animals and of sir-2.1 loss-of-function mutants. Sesamin was also ineffective in bec-1 RNAi-treated animals; bec-1 is a key regulator of autophagy, and is necessary for longevity induced by sir-2.1 overexpression. Furthermore, the heterozygotic mutation of daf-15, which encodes the target of rapamycin (TOR)-binding partner Raptor, abolished lifespan extension by sesamin. Moreover, sesamin did not prolong the lifespan of loss-of-function mutants of aak-2, which encodes the AMP-activated protein kinase (AMPK).
  
  
  CONCLUSIONS
  Sesamin extends the lifespan of C. elegans through several dietary restriction-related signaling pathways, including processes requiring SIRT1, TOR, and AMPK.
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Sugimoto 3-3-138 Sumiyosi-ku, Osaka, Osaka, 558-8585, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Sugimoto 3-3-138 Sumiyosi-ku, Osaka, Osaka, 558-8585, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yaguchi
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Sugimoto 3-3-138 Sumiyosi-ku, Osaka, Osaka, 558-8585, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Komura
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Sugimoto 3-3-138 Sumiyosi-ku, Osaka, Osaka, 558-8585, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakadai
authors.affiliation: CycloChem Co., Ltd., Kobe, 650-0047, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Terao
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Sugimoto 3-3-138 Sumiyosi-ku, Osaka, Osaka, 558-8585, Japan. nakadai@life.osaka-cu.ac.jp.|The OCU Advanced Research Institute for Natural Science and Technology, Osaka City University, Osaka, 558-8585, Japan. nakadai@life.osaka-cu.ac.jp.
authors.forename: Eriko
authors.identifier: http://orcid.org/0000-0001-5068-0460
authors.initials: E
authors.lastname: Kage-Nakadai
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Sugimoto 3-3-138 Sumiyosi-ku, Osaka, Osaka, 558-8585, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction / Q000009:adverse effects*; D019587:Dietary Supplements; D004149:Dioxoles / Q000008:administration & dosage*; D005503:Food Additives / Q000737:chemistry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D064267:Intrinsically Disordered Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000008:administration & dosage*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047408:gamma-Cyclodextrins / Q000737:chemistry
chemical_list: D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D004149:Dioxoles; D005503:Food Additives; D064267:Intrinsically Disordered Proteins; D017705:Lignans; D047408:gamma-Cyclodextrins; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins; C023792:gamma-cyclodextrin; C054125:sesamin
keywords: Caenorhabditis elegans; Dietary restriction; Lifespan; Sesamin