論文

査読有り
2017年1月

Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C-elegans

EXPERIMENTAL GERONTOLOGY
  • Akiko Ihara
  • ,
  • Masaharu Uno
  • ,
  • Koichi Miyatake
  • ,
  • Sakiko Honjoh
  • ,
  • Eisuke Nishida

87
Pt A
開始ページ
40
終了ページ
47
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.exger.2016.10.011
出版者・発行元
PERGAMON-ELSEVIER SCIENCE LTD

Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. (C) 2016 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1016/j.exger.2016.10.011
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27989925
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000393528000006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.exger.2016.10.011
  • ISSN : 0531-5565
  • eISSN : 1873-6815
  • PubMed ID : 27989925
  • Web of Science ID : WOS:000393528000006

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