Quercetin enhances motility in aged and heat-stressed Caenorhabditis elegans nematodes by modulating both HSF-1 activity, and insulin-like and p38-MAPK signalling.

Takaya Sugawara,Kazuichi Sakamoto,Kyung-Jin Min

doi:10.1371/journal.pone.0238528

Abstract

Quercetin is a yellow pigment that is found in many common dietary plants, and that protects against oxidative stress, inflammation, and arteriosclerosis. It has also been suggested to prolong the lifespan of, and enhance heat-stress tolerance in nematodes; thus, the present study investigated its effects on both the nematode life- and health span by assessing its capacity to promote nematode motility after aging and/or heat stress, as well as the mechanisms underlying these effects. The results of the conducted analyses showed that quercetin feeding prolonged lifespan, suppressed age-related motility retardation, improved motility recovery after heat stress, and decreased the production of both intercellular and mitochondrial reactive oxygen species in the analysed Caenorhabditis elegans strains, likely by modulating the insulin-like signalling (ILS) pathway and p38-mitogen-activated protein kinase (MAPK) pathway. In particular, the transcription factors DAF-16 and SKN-1 were found to mediate the observed quercetin-induced effects, consistent with their previously demonstrated roles as regulators of aging. Furthermore, we demonstrated, for the first time, that quercetin induced heat-stress tolerance in C. elegans by modulating HSF-1 expression and/or activity. Thus, the present study provides valuable insights into the mechanisms by which quercetin inhibit aging and enhance heat-stress tolerance via ILS and MAPK pathway in C. elegans.

Highlights

Recent studies have identified a range of biologically active substances in foods; for example, polyphenols such as resveratrol and anthocyanin have been detected in the grape pericarp, and shown to exert strong anti-oxidative effects, and to reduce the risk of arteriosclerosis and stroke [1,2,3]
The C. elegans N2 Bristol, daf-2(e1370), age-1, daf-16, sek-1, hsf-1 (Caenorhabditis Genetics Center (CGC), University of Minnesota, Minneapolis, MN, USA), nsy-1, pmk-1, and skn-1 (National BioResource Project (NBRP), Tokyo Women’s Medical University, Japan) nematode strains were cultured (20 ̊C) on nematode growth medium (NGM) plates that were spread with Escherichia coli (OP50) (Table 1) [22,23]
We investigated whether dimethyl sulfoxide (DMSO) used as solvent has toxicity to the lifespan of nematode and whether 50- and 500μM quercetin used in present study can induce longevity effect to nematode, thereby we designed two controls

Summary

Introduction

Recent studies have identified a range of biologically active substances in foods; for example, polyphenols such as resveratrol and anthocyanin have been detected in the grape pericarp, and shown to exert strong anti-oxidative effects, and to reduce the risk of arteriosclerosis and stroke [1,2,3]. Quercetin used in this study is contained in many different of dietary plants and classified as a flavonoid, one kind of polyphenol. Various flavonoids such as catechin and anthocyanin have been demonstrated to incur physiological effects in many kinds of model organism [4,5].

Methods

Results

Conclusion