Caenorhabditis elegans
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ABSTRACT:
PROVIDER: PRJNA139489 | ENA |
REPOSITORIES: ENA
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Project 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 generates free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. Mammalian NF-E2-related factor 2 (Nrf2) and its C. elegans ortholog SKN-1, mediate protective responses to oxidative stress by promoting target gene expression via antioxidant response elements (ARE). Genetic analyses showed that skn-1 mediates plumbagin’s lifespan-extending effect 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-1-dependent 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.
2012-03-21 | GSE28301 | GEO
Project description:While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.
2022-04-10 | GSE200459 | GEO
Project description:While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.
2021-09-17 | GSE184076 | GEO
Project description:Lifespan extension via eIF4G inhibition is mediated by post-transcriptional remodeling of stress response gene expression in C. elegans
| PRJNA138873 | ENA
Project description:The root of Vicatia thibetica de Boiss is a Chinese herb medicine with homology of medicine and food. We first report that HLB01 (the extract of Vicatia thibetica de Boiss root) extends lifespan and promotes healthy parameters in Caenorhabditis elegans (C. elegans). In doxorubicin-induced senescent mice, HLB01 counteracts senescence associated biomarkers significantly, including AST, ALT, p21 and γH2AX. Interestingly, HLB01 promotes the level of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert anti-aging effects of HLB01. In addition, HLB01 can scavenge free radical to perform antioxidant ability. Lifespan extension of HLB01 also dependent on DAF-16 and HSF-1 to perform oxidative stress resistance and heat stress resistance. Taken together, these data indicate that HLB01 extends lifespan and healthspan of C. elegans, resists doxorubicin‐induced senescence in mice via collagen promoting, antioxidant and stress resistance.
2021-03-06 | GSE168322 | GEO
Project description:Ribose-5-phosphate isomerase A (RPIA) is a rate-limiting enzyme, which connects oxidative phase to non-oxidative phase and mediates redox homeostasis in pentose phosphate pathway (PPP). Here, we report that spatially and temporally limited knockdown of rpia-1 prolongs lifespan and improves healthspan in C. elegans, reflecting the evolutionarily conserved phenotypes observed in Drosophila. We first confirmed that both ubiquitous (in N2) and pan-neuronal (in TU3401) knockdown of rpia-1 enhance tolerance to oxidative stress, reduce polyglutamine aggregation, and improve the deteriorated body bending rate caused by polyglutamine aggregation. Next, we observed that both rpia-1 knockdown conditions enhance lifespan. In addition, rpia-1 knockdown in glutamatergic or cholinergic neurons was sufficient to increase lifespan. Besides the regulation of healthspan through the elevation of NADPH levels, we also identified novel molecular mechanisms that contribute to the longevity effect. Our results showed that rpia-1 reduction was accompanied by induction of autophagic flux, activation of AMPK, and inhibition of TOR signaling. Importantly, the lifespan extension by rpia-1 knockdown required the activation of autophagy and AMPK pathways, and reduced TOR sig-naling. Moreover, the RNA-seq data from the two longlived rpia-1 knockdown strains supported our experimental findings and reveal potential downstream targets, which may play key roles in this intervention. Together, our data disclose the specific spatial and temporal conditions and the underlying molecular mechanisms of rpia-1 knockdown-mediated longevity in C. elegans. These findings may facilitate the development of translational medicine and the improvement of lon-gevity research.
2023-01-25 | GSE216697 | GEO
Project description:Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendents. The histone H3 lysine 4 trimethylation (H3K4me3) complex composed of ASH-2, WDR-5, and the histone methyltransferase SET-2 regulates C. elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5, or SET-2 in the parental generation extend the lifespan of descendents up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendents. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendents.
2011-10-19 | GSE31043 | GEO
Project description:Aging is under genetic control in C. elegans but the mechanisms of lifespan regulation are not completely known. MicroRNAs (miRNAs) regulate various aspects of development and metabolism and one miRNA has been previously implicated in lifespan. Here we show that multiple miRNAs change expression in C. elegans aging, including novel miRNAs, and that mutations in several of the most up-regulated miRNAs lead to lifespan defects. Some act to promote normal lifespan and stress resistance while others inhibit these phenomena. We find that these miRNAs genetically interact with genes in the DNA damage checkpoint response pathway and in the insulin signaling pathway. Our findings reveal that miRNAs both positively and negatively influence lifespan. Since several miRNAs up-regulated during aging regulate genes in conserved pathways of aging and thereby influence lifespan in C. elegans, we propose that miRNAs may play important roles in stress response and aging of more complex organisms. 4 sample examined: Wild-type (N2) and long-lived daf-2(e1379) animals at days 0 and 10 of adulthood
2011-01-01 | E-GEOD-24510 | biostudies-arrayexpress
Project description:How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in C.CaenorhabditisC. elegans elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity.
2020-04-03 | GSE128935 | GEO
Project description:We have previously reported that tyrosol (TYR), one of the main phenols in extra virgin olive oil (EVOO), promotes lifespan extension in the nematode Caenorhabditis elegans, also inducing a stronger resistance to thermal and oxidative stress in this animal model. Although the influence of several longevity-related genes in these effects has been reported by our group, we decided to perform a whole genome DNA-microarray approach in order to identify other genes and molecular pathways further involved in TYR effects on C. elegans longevity. Microarray analysis identified 208 differentially expressed genes (206 overexpressed and 2 underexpressed) when comparing TYR-treated nematodes with non-treated controls. Many of these genes seem linked to processes such as regulation of growth, transcription, reproduction, lipid metabolism and body morphogenesis. Data obtained by microarray was validated by qRT-PCR analysis of selected genes. Our results confirm that several important cellular mechanisms related to longevity are influenced by TYR treatment in this animal model. Moreover, we detected an interesting overlap between the expression pattern elicited by TYR and those induced by other dietary polyphenols known to extend lifespan in C. elegans, such as quercetin and tannic acid.
2014-11-01 | GSE57664 | GEO