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Sesamin extends lifespan through pathways related to dietary restriction in Caenorhabditis elegans

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Abstract

Purpose

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.

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Acknowledgements

We thank the Caenorhabditis Genetics Center (University of Minnesota, Minneapolis, MN; supported by the National Institutes of Health-National Center for Research Resources) for providing C. elegans strains, and M. Doe for supporting the NMR analyses. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) (to Y.N.) and by a Grant-in-Aid for young scientists from the JSPS (to E.K-N.).

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Authors and Affiliations

  1. Graduate School of Human Life Science, Osaka City University, Sugimoto 3-3-138 Sumiyosi-ku, Osaka, Osaka, 558-8585, Japan

    Yumiko Nakatani, Yukie Yaguchi, Tomomi Komura, Masakazu Nakadai, Eriko Kage-Nakadai & Yoshikazu Nishikawa

  2. CycloChem Co., Ltd., Kobe, 650-0047, Japan

    Kenji Terao

  3. The OCU Advanced Research Institute for Natural Science and Technology, Osaka City University, Osaka, 558-8585, Japan

    Eriko Kage-Nakadai

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  1. Yumiko Nakatani
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  2. Yukie Yaguchi
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  3. Tomomi Komura
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  4. Masakazu Nakadai
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Correspondence to Eriko Kage-Nakadai.

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Nakatani, Y., Yaguchi, Y., Komura, T. et al. Sesamin extends lifespan through pathways related to dietary restriction in Caenorhabditis elegans . Eur J Nutr 57, 1137–1146 (2018). https://doi.org/10.1007/s00394-017-1396-0

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