| Citation | Hunt PR, Son TG, Wilson MA, Yu QS, Wood WH, Zhang Y, Becker KG, Greig NH, Mattson MP, Camandola S, Wolkow CA. Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms. PLoS One, 2011. |
| PubMed ID | 21765926 |
| Short Description | Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms. GEO Record: GSE28301 Platform: GPL7727 Download gene-centric, log2 transformed data: WBPaper00039878.ce.mr.csv |
| # of Conditions | 8 |
Full Description
|
Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC) transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway. Experimental Details: WBPaper00039878:DMSO_rep1 WBPaper00039878:PLB_rep1 WBPaper00039878:DMSO_rep2 WBPaper00039878:PLB_rep2 WBPaper00039878:DMSO_rep3 WBPaper00039878:PLB_rep3 WBPaper00039878:DMSO_rep4 WBPaper00039878:PLB_rep4. |
|
Tags
|
Contact: help (at) wormbase.org
