論文

査読有り
2009年2月

Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C-elegans

NATURE
  • Sakiko Honjoh
  • ,
  • Takuya Yamamoto
  • ,
  • Masaharu Uno
  • ,
  • Eisuke Nishida

457
7230
開始ページ
726
終了ページ
U6
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/nature07583
出版者・発行元
NATURE PUBLISHING GROUP

Dietary restriction is the most effective and reproducible intervention to extend lifespan in divergent species(1). In mammals, two regimens of dietary restriction, intermittent fasting ( IF) and chronic caloric restriction, have proven to extend lifespan and reduce the incidence of age- related disorders(2). An important characteristic of IF is that it can increase lifespan even when there is little or no overall decrease in calorie intake(2). The molecular mechanisms underlying IF- induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that the low molecular weight GTPase RHEB- 1 has a dual role in lifespan regulation; RHEB- 1 is required for the IF- induced longevity, whereas inhibition of RHEB- 1 mimics the caloric- restriction effects. RHEB- 1 exerts its effects in part by the insulin/ insulin growth factor ( IGF)- like signalling effector DAF- 16 in IF. Our analyses demonstrate that most fasting- induced upregulated genes require RHEB- 1 function for their induction, and that RHEB- 1 and TOR signalling are required for the fasting- induced downregulation of an insulin- like peptide, INS- 7. These findings identify the essential role of signalling by RHEB- 1 in IF- induced longevity and gene expression changes, and suggest a molecular link between the IF- induced longevity and the insulin/ IGF- like signalling pathway.

Web of Science ® 被引用回数 : 160

リンク情報
DOI
https://doi.org/10.1038/nature07583
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19079239
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000263064700042&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/nature07583
  • ISSN : 0028-0836
  • eISSN : 1476-4687
  • PubMed ID : 19079239
  • Web of Science ID : WOS:000263064700042

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