Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan

Broccoli-derived isothiocyanate sulforaphane inhibits inflammation and cancer. Sulforaphane may support healthy aging, but the underlying detailed mechanisms are unclear. We used the C. elegans nematode model to address this question. Wild-type and 4 mutant C. elegans worm strains were fed in the pr...

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Autores principales:	Huihui Ji, Zhimin Qi, Daniel Schrapel, Monika Le, Yiqiao Luo, Bin Yan, Jury Gladkich, Michael Schaefer, Li Liu, Ingrid Herr
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	sulforaphane aging C. elegans TRA-1/GLI DAF-16/FOXO Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3afcecfa695644f9942df44b98c6a16c
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spelling	oai:doaj.org-article:3afcecfa695644f9942df44b98c6a16c2021-12-03T06:29:33ZSulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan2296-634X10.3389/fcell.2021.784999https://doaj.org/article/3afcecfa695644f9942df44b98c6a16c2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.784999/fullhttps://doaj.org/toc/2296-634XBroccoli-derived isothiocyanate sulforaphane inhibits inflammation and cancer. Sulforaphane may support healthy aging, but the underlying detailed mechanisms are unclear. We used the C. elegans nematode model to address this question. Wild-type and 4 mutant C. elegans worm strains were fed in the presence or absence of sulforaphane and E. coli food bacteria transfected with RNA interference gene constructs. Kaplan–Meier survival analysis, live imaging of mobility and pharyngeal pumping, fluorescence microscopy, RT–qPCR, and Western blotting were performed. In the wild type, sulforaphane prolonged lifespan and increased mobility and food intake because of sulforaphane-induced upregulation of the sex-determination transcription factor TRA-1, which is the ortholog of the human GLI mediator of sonic hedgehog signaling. In turn, the tra-1 target gene daf-16, which is the ortholog of human FOXO and the major mediator of insulin/IGF-1 and aging signaling, was induced. By contrast, sulforaphane did not prolong lifespan and healthspan when tra-1 or daf-16 was inhibited by RNA interference or when worms with a loss-of-function mutation of the tra-1 or daf-16 genes were used. Conversely, the average lifespan of C. elegans with hyperactive TRA-1 increased by 8.9%, but this longer survival was abolished by RNAi-mediated inhibition of daf-16. Our data suggest the involvement of sulforaphane in regulating healthy aging and prolonging lifespan by inducing the expression and nuclear translocation of TRA-1/GLI and its downstream target DAF-16/FOXO.Huihui JiZhimin QiDaniel SchrapelMonika LeYiqiao LuoBin YanJury GladkichMichael SchaeferLi LiuIngrid HerrFrontiers Media S.A.articlesulforaphaneagingC. elegansTRA-1/GLIDAF-16/FOXOBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sulforaphane aging C. elegans TRA-1/GLI DAF-16/FOXO Biology (General) QH301-705.5
spellingShingle	sulforaphane aging C. elegans TRA-1/GLI DAF-16/FOXO Biology (General) QH301-705.5 Huihui Ji Zhimin Qi Daniel Schrapel Monika Le Yiqiao Luo Bin Yan Jury Gladkich Michael Schaefer Li Liu Ingrid Herr Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan
description	Broccoli-derived isothiocyanate sulforaphane inhibits inflammation and cancer. Sulforaphane may support healthy aging, but the underlying detailed mechanisms are unclear. We used the C. elegans nematode model to address this question. Wild-type and 4 mutant C. elegans worm strains were fed in the presence or absence of sulforaphane and E. coli food bacteria transfected with RNA interference gene constructs. Kaplan–Meier survival analysis, live imaging of mobility and pharyngeal pumping, fluorescence microscopy, RT–qPCR, and Western blotting were performed. In the wild type, sulforaphane prolonged lifespan and increased mobility and food intake because of sulforaphane-induced upregulation of the sex-determination transcription factor TRA-1, which is the ortholog of the human GLI mediator of sonic hedgehog signaling. In turn, the tra-1 target gene daf-16, which is the ortholog of human FOXO and the major mediator of insulin/IGF-1 and aging signaling, was induced. By contrast, sulforaphane did not prolong lifespan and healthspan when tra-1 or daf-16 was inhibited by RNA interference or when worms with a loss-of-function mutation of the tra-1 or daf-16 genes were used. Conversely, the average lifespan of C. elegans with hyperactive TRA-1 increased by 8.9%, but this longer survival was abolished by RNAi-mediated inhibition of daf-16. Our data suggest the involvement of sulforaphane in regulating healthy aging and prolonging lifespan by inducing the expression and nuclear translocation of TRA-1/GLI and its downstream target DAF-16/FOXO.
format	article
author	Huihui Ji Zhimin Qi Daniel Schrapel Monika Le Yiqiao Luo Bin Yan Jury Gladkich Michael Schaefer Li Liu Ingrid Herr
author_facet	Huihui Ji Zhimin Qi Daniel Schrapel Monika Le Yiqiao Luo Bin Yan Jury Gladkich Michael Schaefer Li Liu Ingrid Herr
author_sort	Huihui Ji
title	Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan
title_short	Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan
title_full	Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan
title_fullStr	Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan
title_full_unstemmed	Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan
title_sort	sulforaphane targets tra-1/gli upstream of daf-16/foxo to promote c. elegans longevity and healthspan
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3afcecfa695644f9942df44b98c6a16c
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Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan

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