scholarly journals The symbiotic relationship between Caenorhabditis elegans and members of its microbiome contributes to worm fitness and lifespan extension

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Orçun Haçariz ◽  
Charles Viau ◽  
Farial Karimian ◽  
Jianguo Xia
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathways ◽  
Vitamin B6 ◽  
Genomic Diversity ◽  
Glutathione Metabolism ◽  
Lifespan Extension ◽  
Promising Alternative ◽  
Host Fitness ◽  
C Elegans ◽  
Cellular Detoxification

Abstract Background A healthy microbiome influences host physiology through a mutualistic relationship, which can be important for the host to cope with cellular stress by promoting fitness and survival. The mammalian microbiome is highly complex and attributing host phenotypes to a specific member of the microbiome can be difficult. The model organism Caenorhabditis elegans and its native microbiome, discovered recently, can serve as a more tractable, experimental model system to study host-microbiome interactions. In this study, we investigated whether certain members of C. elegans native microbiome would offer a benefit to their host and putative molecular mechanisms using a combination of phenotype screening, omics profiling and functional validation. Results A total of 16 members of C. elegans microbiome were screened under chemically-induced toxicity. Worms grown with Chryseobacterium sp. CHNTR56 MYb120 or Comamonas sp. 12022 MYb131, were most resistant to oxidative chemical stress (SiO2 nanoparticles and juglone), as measured by progeny output. Further investigation showed that Chryseobacterium sp. CHNTR56 positively influenced the worm’s lifespan, whereas the combination of both isolates had a synergistic effect. RNAseq analysis of young adult worms, grown with either isolate, revealed the enrichment of cellular detoxification mechanisms (glutathione metabolism, drug metabolism and metabolism of xenobiotics) and signaling pathways (TGF-beta and Wnt signaling pathways). Upregulation of cysteine synthases (cysl genes) in the worms, associated with glutathione metabolism, was also observed. Nanopore sequencing uncovered that the genomes of the two isolates have evolved to favor the specific route of the de novo synthesis pathway of vitamin B6 (cofactor of cysl enzymes) through serC or pdxA2 homologs. Finally, co-culture with vitamin B6 extended worm lifespan. Conclusions In summary, our study indicates that certain colonizing members of C. elegans have genomic diversity in vitamin B6 synthesis and promote host fitness and lifespan extension. The regulation of host cellular detoxification genes (i.e. gst) along with cysl genes at the transcriptome level and the bacterium-specific vitamin B6 synthesis mechanism at the genome level are in an agreement with enhanced host glutathione-based cellular detoxification due to this interspecies relationship. C. elegans is therefore a promising alternative model to study host-microbiome interactions in host fitness and lifespan.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals Piceatannol, a Natural Stilbene, Extends the Lifespan of Caenorhabditis elegans Under Fasting Through Inhibition of Lipolysis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 38-38
Author(s):  
Jang Miran ◽  
Zhang Yuan ◽  
Bai Juan ◽  
Jun-Bae An ◽  
Park Yeonhwa ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Caenorhabditis Elegans ◽  
Negative Energy ◽  
Hormone Sensitive Lipase ◽  
Pcr Analysis ◽  
Lifespan Extension ◽  
Mrna Levels ◽  
Free Glycerol ◽  
C Elegans ◽  
Glycerol Level

Abstract Objectives Lipolysis is the catabolic process that hydrolyzes triglyceride (TG) to free fatty acids (FFAs) and glycerol under negative energy balance such as fasting. In adipocytes, adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase play key roles in a series of TG hydrolysis reactions in mammals. However, overly activated adipose lipolysis is believed to contribute to link between obesity and systemic inflammation and oxidative stress. We previously demonstrated that piceatannol (PIC), a natural resveratrol analogue, inhibits adipogenesis in cultured adipocytes and lipogenesis in Caenorhabditis elegans. Furthermore, we showed that PIC extends the lifespan of C. elegans via the insulin/IGF-1 signaling. However, the effects of PIC on lipid metabolism during fasting state is unknown. Methods We conducted Oil-Red-O assay, Enzyme assay (TG and Free glycerol contents), PCR analysis and lifespan assay. Results In this study, we demonstrated that PIC-treated C. elegans exhibited suppressed lipolysis under fasting as judged by increased lipid accumulation and TG levels with decreased free glycerol level. Consistent with these findings, PIC treatment resulted in decreased mRNA levels of genes involved lipolysis such as atgl-1, hosl-1 and aak-2 in fasted C. elegans. Also, PIC treatment augmented fasting-induced lifespan of C. elegans by an increased daf-16 gene expression. However, such effect was abolished when atgl-1, aak-2, and daf-16 mutants were treated with PIC. In addition, we also found that autophagy is required for PIC-induced lifespan in C. elegans during fasting since autophagy inhibitor treatments and autophagy gene deficient worms resulted in blunting the lifespan extension effect of PIC. Conclusions Collectively, our results indicate that PIC contributes to lifespan extension in C. elegans during fasting possibly through regulating lipolysis- and/or autophagy-dependent lipid metabolism. Funding Sources 1. The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2019R1A2C1086146) and (2019R1A6A3A03033878) 2. The Rural Development Administration of the Republic of Korea.

scholarly journals Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wenwen Liu ◽  
Yunhui Guan ◽  
Sicong Qiao ◽  
Jiqun Wang ◽  
Keting Bao ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Chinese Herb ◽  
Premature Aging ◽  
Lifespan Extension ◽  
Root Extract ◽  
Antioxidant Ability ◽  
C Elegans ◽  
Adult Mice ◽  
Heat Stress Resistance

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.

scholarly journals DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 109 ◽  
Author(s):  
Aleksandra Zečić ◽  
Bart P. Braeckman
Keyword(s):  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Antioxidant Defense ◽  
Lifespan Extension ◽  
Metabolic Shift ◽  
Glyoxylate Shunt ◽  
C Elegans ◽  
Forkhead Box ◽  
Metabolic Remodeling ◽  
Transcriptional Changes

DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in Caenorhabditis elegans, integrates signals from upstream pathways to elicit transcriptional changes in many genes involved in aging, development, stress, metabolism, and immunity. The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In C. elegans daf-2 mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood. This program includes elevated antioxidant defense and a metabolic shift toward accumulation of carbohydrates (i.e., trehalose and glycogen) and triglycerides, and activation of the glyoxylate shunt, which could allow fat-to-carbohydrate conversion. The longevity of daf-2 mutants seems to be partially supported by endogenous trehalose, a nonreducing disaccharide that mammals cannot synthesize, which points toward considerable differences in downstream mechanisms by which IIS regulates aging in distinct groups.

scholarly journals Untangling Longevity, Dauer, and Healthspan in Caenorhabditis elegans Insulin/IGF-1-Signalling

Gerontology ◽  
2017 ◽  
Vol 64 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Collin Yvès Ewald ◽  
Jorge Iván Castillo-Quan ◽  
T. Keith Blackwell
Keyword(s):  
Caenorhabditis Elegans ◽  
Healthy Aging ◽  
Receptor Gene ◽  
Recent Analysis ◽  
Lifespan Extension ◽  
Extension Programs ◽  
Subsequent Work ◽  
C Elegans ◽  
Downstream Processes ◽  
Shed Light

The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C. elegans to endure harsh environments through morphological adaptation, improved cellular repair, and slowed metabolism. Considerable progress has been made uncovering mechanisms that are affected by C. elegans rIIS. However, from the beginning it has remained unclear to what extent rIIS extends C. elegans lifespan by mobilizing dauer-associated mechanisms in adults. As we discuss, recent work has shed light on this question by determining that rIIS can extend C. elegans lifespan comparably through downstream processes that are either dauer-related or -independent. Importantly, these two lifespan extension programs can be distinguished genetically. It will now be critical to tease apart these programs, because each may involve different longevity-promoting mechanisms that may be relevant to higher organisms. A recent analysis of organismal “healthspan” has questioned the value of C. elegans rIIS as a paradigm for understanding healthy aging, as opposed to simply extending life. We discuss other work that argues strongly that C. elegans rIIS is indeed an invaluable model and consider the likely possibility that dauer-related processes affect parameters associated with health under rIIS conditions. Together, these studies indicate that C. elegans and analyses of rIIS in this organism will continue to provide unexpected and exciting results, and new paradigms that will be valuable for understanding healthy aging in humans.

scholarly journals Specificity and Complexity of the Caenorhabditis elegans Innate Immune Response

2007 ◽  
Vol 27 (15) ◽  
pp. 5544-5553 ◽  
Author(s):  
Scott Alper ◽  
Sandra J. McBride ◽  
Brad Lackford ◽  
Jonathan H. Freedman ◽  
David A. Schwartz
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Signaling Pathways ◽  
Large Set ◽  
Immune Signaling ◽  
C Elegans ◽  
Immunity Genes ◽  
Simple Model System ◽  
Overlapping Sets

ABSTRACT In response to infection, Caenorhabditis elegans produces an array of antimicrobial proteins. To understand the C. elegans immune response, we have investigated the regulation of a large, representative sample of candidate antimicrobial genes. We found that all these putative antimicrobial genes are expressed in tissues exposed to the environment, a position from which they can ward off infection. Using RNA interference to inhibit the function of immune signaling pathways in C. elegans, we found that different immune response pathways regulate expression of distinct but overlapping sets of antimicrobial genes. We also show that different bacterial pathogens regulate distinct but overlapping sets of antimicrobial genes. The patterns of genes induced by pathogens do not coincide with any single immune signaling pathway. Thus, even in this simple model system for innate immunity, striking specificity and complexity exist in the immune response. The unique patterns of antimicrobial gene expression observed when C. elegans is exposed to different pathogens or when different immune signaling pathways are perturbed suggest that a large set of yet to be identified pathogen recognition receptors (PRRs) exist in the nematode. These PRRs must interact in a complicated fashion to induce a unique set of antimicrobial genes. We also propose the existence of an “antimicrobial fingerprint,” which will aid in assigning newly identified C. elegans innate immunity genes to known immune signaling pathways.

scholarly journals Natural genetic variation drives microbiome selection in the Caenorhabditis elegans gut

2021 ◽  
Author(s):  
Fan Zhang ◽  
Jessica L. Weckhorst ◽  
Adrien Assié ◽  
Ciara Hosea ◽  
Christopher A. Ayoub ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Natural Genetic Variation ◽  
Microbiome Composition ◽  
C Elegans ◽  
Free Living Nematode ◽  
Wild Strains ◽  
The Stability

Host genetic landscapes can shape microbiome assembly in the animal gut by contributing to the establishment of distinct physiological environments. However, the genetic determinants contributing to the stability and variation of these microbiome types remain largely undefined. Here, we use the free-living nematode Caenorhabditis elegans to identify natural genetic variation among wild strains of C. elegans strains that drives assembly of distinct microbiomes. To achieve this, we first established a diverse model microbiome that represents the phylogenetic and functional diversity naturally found in the C. elegans microbiome. Using this community, we show that C. elegans utilizes immune, xenobiotic and metabolic signaling pathways to favor the assembly of different microbiome types. Variations in these pathways were associated with the enrichment for specific commensals, including the Alphaproteobacteria Ochrobactrum. Using RNAi and mutant strains, we showed that host selection for Ochrobactrum is mediated specifically by host insulin signaling pathways. Ochrobactrum recruitment is blunted in the absence of daf-2/IGFR and requires the insulin signaling transcription factors daf-16/FOXO and pqm-1/SALL2. Further, the ability of C. elegans to enrich for Ochrobactrum is correlated positively with host outcomes, as animals that develop faster are larger and have higher gut Ochrobactrum colonization as adults. These results highlight a new role for the highly conserved insulin signaling pathways in the regulation of microbiome composition in C. elegans.

scholarly journals Lifespan extension in Caenorhabditis elegans insulin/IGF-1 signalling mutants is supported by non-vertebrate physiological traits

Nematology ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. 499-508
Author(s):  
Bart P. Braeckman ◽  
Ineke Dhondt
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Causal Relation ◽  
Glyoxylate Cycle ◽  
Protein Carbonyls ◽  
Lifespan Extension ◽  
Turnover Rates ◽  
C Elegans ◽  
Trehalose Synthesis

The insulin/IGF-1 signalling (IIS) pathway connects nutrient levels to metabolism, growth and lifespan in eukaryotes ranging from yeasts to humans, including nematodes such as the genetic model organismCaenorhabditis elegans. The link between ageing and the IIS pathway has been thoroughly studied inC. elegans; upon reduced IIS signalling, a genetic survival program is activated resulting in a drastic lifespan extension. One of the components of this program is the upregulation of antioxidant activity but experiments failed to show a clear causal relation to longevity. However, oxidative damage, such as protein carbonyls, accumulates at a slower pace in long-livedC. elegansmutants with reduced IIS. This is probably not achieved by increased macroautophagy, a process that sequesters cellular components to be eliminated as protein turnover rates are slowed down in IIS mutants. The IIS mutantdaf-2, bearing a mutation in the insulin/IGF-1 receptor, recapitulates the dauer survival program, including accumulation of fat and glycogen. Fat can be converted into glucose and glycogenviathe glyoxylate shunt, a pathway absent in vertebrates. These carbohydrates can be used as substrates for trehalose synthesis, also absent in mammals. Trehalose, a non-reducing homodimer of glucose, stabilises intracellular components and is responsible for almost half of the lifespan extension in IIS mutants. Hence, the molecular mechanisms by which lifespan is extended under reduced IIS may differ substantially between phyla that have an active glyoxylate cycle and trehalose synthesis, such as ecdysozoans and fungi, and vertebrate species such as mammals.

scholarly journals Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9

2021 ◽  
Author(s):  
Keting Bao ◽  
Jiali Feng ◽  
Wenwen Liu ◽  
Zhifan Mao ◽  
Tianyue Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Lifespan Extension ◽  
Aging Effects ◽  
Hypertonic Stress ◽  
C Elegans ◽  
Promising Application ◽  
Application Prospects

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.

scholarly journals Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jessica T Chang ◽  
Caroline Kumsta ◽  
Andrew B Hellman ◽  
Linnea M Adams ◽  
Malene Hansen
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Wall ◽  
Lifespan Extension ◽  
Autophagic Flux ◽  
Wild Type ◽  
C Elegans ◽  
Spatiotemporal Regulation ◽  
Age Related ◽  
Autophagic Activity ◽  
Underlying Mechanisms

Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals. In contrast, daf-2 and glp-1 mutants displayed unique age- and tissue-specific changes in autophagic activity, indicating that the two longevity paradigms have distinct effects on autophagy during aging. Although autophagy appeared active in the intestine of both long-lived mutants, inhibition of intestinal autophagy significantly abrogated lifespan extension only in glp-1 mutants. Collectively, our data suggest that autophagic activity normally decreases with age in C. elegans, whereas daf-2 and glp-1 long-lived mutants regulate autophagy in distinct spatiotemporal-specific manners to extend lifespan.

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