title: Influence of oral supplementation with sesamin on longevity of Caenorhabditis elegans and the host defense.
abstract: OBJECTIVE
  Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans.
  
  
  METHODS
  Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects.
  
  
  RESULTS
  Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev-1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf-2, daf-16, pmk-1, and skn-1.
  
  
  CONCLUSIONS
  Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn-1 (encoding a component of the p38 MAPK pathway) and daf-16 (encoding a component of the IGF-1 pathway).
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yaguchi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Komura
authors.forename: Noriko
authors.initials: N
authors.lastname: Kashima
authors.forename: Miho
authors.initials: M
authors.lastname: Tamura
authors.forename: Eriko
authors.initials: E
authors.lastname: Kage-Nakadai
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saeki
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology*; D004926:Escherichia coli; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D016952:Legionella pneumophila; D017705:Lignans / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000502:physiology; D019779:Salmonella enterica; D015398:Signal Transduction; D047408:gamma-Cyclodextrins / Q000008:administration & dosage; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004149:Dioxoles; D017705:Lignans; D047408:gamma-Cyclodextrins; D007334:Insulin-Like Growth Factor I; D048051:p38 Mitogen-Activated Protein Kinases; C023792:gamma-cyclodextrin; C054125:sesamin