title: Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.
abstract: BACKGROUND
  One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action.
  
  
  RESULTS
  We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity.
  
  
  CONCLUSIONS
  These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical interventions in the aging process.
authors.affiliation: Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Sakaecho, Itabashiku, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Honda
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujita
authors.forename: Hiroe
authors.initials: H
authors.lastname: Maruyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Araki
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichihara
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Shuji
authors.initials: S
authors.lastname: Honda
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000375:Aging / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D000818:Animals; D001516:Bees / Q000737:chemistry; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002845:Chromatography / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099219:Royal Jelly
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins; D010447:Peptide Hydrolases; D014157:Transcription Factors; D000099219:Royal Jelly; C108831:daf-16 protein, C elegans; C055543:10-hydroxy-2-decenoic acid