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Caenorhabditis elegans: A Model Organism for Human Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (20 May 2025) | Viewed by 4505

Special Issue Editor

Dr. Andreia Teixeira-Castro

E-Mail Website
Guest Editor
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal
Interests: C. elegans; disease model; neurodegenerative disorder

Special Issue Information

Dear Colleagues,

The nematode Caenorhabditis elegans offers unique advantages that enable comprehensive research of the cellular and molecular mechanisms underlying human physiology, as well as devastating human pathologies, including neurodevelopmental diseases, age-associated neurodegenerative and neuromuscular disorders, stroke, and cancer.

The tiny worm proved pivotal in uncovering novel cellular mechanisms, including the Nobel prize-winning discoveries of programmed cell death, RNA interference, and the discovery and development of the Green Fluorescent Protein.

The evolutionary conservation between C. elegans and humans led to the establishment of robust C. elegans models of human diseases that closely mimic core disease-related phenotypes. These models allow studies from single-cell resolution to intra- and inter-tissue communication, whole-organism responses to internal and external stimuli, and large-scale genetic and pharmacological screenings. These are designed to elucidate the molecular mechanisms mediating pathogenesis and to identify and validate targets and drugs for emergent therapeutic interventions.

This Special Issue aims to provide an overview of the current research using C. elegans to study all aspects of human health and disease. It also celebrates the 50th anniversary of Sidney Brenner’s seminal paper on the identification of mutations that affect whole-animal behavior, priming a series of groundbreaking scientific discoveries.

Dr. Andreia Teixeira-Castro
Guest Editor

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Keywords

  • human physiology
  • human disease
  • therapy
  • novel C. elegans methods
  • novel C. elegans models
  • disease models

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Published Papers (4 papers)

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Research

19 pages, 4912 KiB  
Article
Therapeutic Effects of Hemerocallis citrina Baroni Extract on Animal Models of Neurodegenerative Diseases Through Serotonin and HLH-30/TFEB-Dependent Mechanisms
by Jorge H. Fernandes, Marta Daniela Costa, Daniela Vilasboas-Campos, Bruna Ferreira-Lomba, Joana Pereira-Sousa, Qiong Wang, Andreia Teixeira-Castro, Xinmin Liu, Fengzhong Wang, Alberto C. P. Dias and Patrícia Maciel
Int. J. Mol. Sci. 2025, 26(9), 4145; https://doi.org/10.3390/ijms26094145 - 27 Apr 2025
Viewed by 292
Abstract
Hemerocallis citrina is an herbaceous perennial plant used in Asian cuisine and Traditional Chinese Medicine. Here, we tested the therapeutic potential of extracts (HCE30%, HCE50%, and HCN) in vivo, using models of two human genetic neurodegenerative diseases—Machado–Joseph Disease/Spinocerebellar Ataxia type 3 (MJD/SCA3) and [...] Read more.
Hemerocallis citrina is an herbaceous perennial plant used in Asian cuisine and Traditional Chinese Medicine. Here, we tested the therapeutic potential of extracts (HCE30%, HCE50%, and HCN) in vivo, using models of two human genetic neurodegenerative diseases—Machado–Joseph Disease/Spinocerebellar Ataxia type 3 (MJD/SCA3) and Frontotemporal Dementia with Parkinsonism associated to chromosome 17 (FTDP-17). Chronic treatment with HCE30% extract ameliorated the motor deficits typically observed in these models. Interestingly, we found that the effect on the motor phenotype of the MJD/SCA3 model was dependent on serotonergic signaling and on the action of the HLH-30/TFEB transcription factor, known to regulate the cellular response to amino acid starvation, the autophagy and mitophagy pathways, lysosome localization and biogenesis, exocytosis, and mitochondrial biogenesis. Altogether, our findings reinforce the idea that phytochemicals act through the modulation of serotonergic neurotransmission and introduce a novel layer to the HLH-30/TFEB regulatory network. Thus, it also strengthens the use of these pathways as therapeutic targets for protein-related neurodegenerative disorders and confirms the utility of medicinal plants as a source of innovation in the quest for new therapeutic agents. Full article
(This article belongs to the Special Issue Caenorhabditis elegans: A Model Organism for Human Health and Disease)
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23 pages, 2128 KiB  
Article
Maral Root Extract and Its Main Constituent 20-Hydroxyecdysone Enhance Stress Resilience in Caenorhabditis elegans
by Velislava Todorova, Monika N. Todorova, Martina S. Savova, Kalin Ivanov, Milen I. Georgiev and Stanislava Ivanova
Int. J. Mol. Sci. 2025, 26(8), 3739; https://doi.org/10.3390/ijms26083739 - 15 Apr 2025
Viewed by 507
Abstract
As human life expectancy continues to rise, managing age-related diseases and preserving health in later years remain significant challenges. Consequently, there is a growing demand for strategies that enhance both the quality and the duration of life. Interventions that promote longevity, particularly those [...] Read more.
As human life expectancy continues to rise, managing age-related diseases and preserving health in later years remain significant challenges. Consequently, there is a growing demand for strategies that enhance both the quality and the duration of life. Interventions that promote longevity, particularly those derived from natural sources, are popular for their potential to address age-related health concerns. Adaptogens—herbs, roots, and mushrooms—are valued in food science and nutrition for their ability to enhance resilience and overall well-being. Among these, Rhaponticum carthamoides (Willd.) Iljin, known as maral root (Russian leuzea), holds a prominent place in Siberian traditional medicine. The root extract, abundant in bioactive compounds such as flavonoids and phytoecdysteroids, is reputed for reducing fatigue, boosting strength, and offering immunomodulatory benefits. However, the effects of the plant extract on lifespan and age-related decline remains poorly studied. This study investigates the effect of maral root extract and phytoecdysteroids—ecdysterone, ponasterone, and turkesterone—on aging using Caenorhabditis elegans as a model organism. A sensitive liquid chromatography method with photodiode array detection was developed and validated to quantify the phytoecdysteroids in the extract. Behavioural and stress-response assays revealed that maral root not only extends lifespan but also significantly enhanced healthspan, stress resilience, and fitness in the nematodes. Additionally, treatment with ecdysterone, the most abundant compound in the root extract, improved healthspan by enhancing stress response. These findings underscore the potential of maral root as a natural adaptogen to mitigate age-related decline, providing valuable insights into natural longevity interventions. Full article
(This article belongs to the Special Issue Caenorhabditis elegans: A Model Organism for Human Health and Disease)
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12 pages, 932 KiB  
Communication
Caenorhabditis elegans as a Model to Assess the Potential Risk to Human Health Associated with the Use of Bisphenol A and Its Substitutes
by Alžbeta Kaiglová, Zuzana Bárdyová, Patrícia Hockicková, Aneta Zvolenská, Kamila Melnikov and Soňa Kucharíková
Int. J. Mol. Sci. 2025, 26(5), 2013; https://doi.org/10.3390/ijms26052013 - 25 Feb 2025
Viewed by 582
Abstract
Given its simplicity, Caenorhabditis elegans appears to be a promising model for future research on endocrine disruptors, including bisphenol A and its supposedly safer alternatives. The aim of this study was to investigate the impact of embryonic exposure of C. elegans to different [...] Read more.
Given its simplicity, Caenorhabditis elegans appears to be a promising model for future research on endocrine disruptors, including bisphenol A and its supposedly safer alternatives. The aim of this study was to investigate the impact of embryonic exposure of C. elegans to different concentrations (0.5, 1.0, and 5 µM) of bisphenol A and its analogs (bisphenol S, bisphenol F, and bisphenol AF) on selected biological characteristics of the nematode C. elegans and to compare them with an unexposed control group. Embryonal exposure of C. elegans to bisphenol A, as well as bisphenol S, F, and AF at concentrations of 0.5, 1.0, and 5 µM resulted in a significant influence on the percentage of hatched eggs and habituation to anterior stimuli (with significant results ranging from p ≤ 0.05 to p ≤ 0.001). The growth of C. elegans was also significantly impaired by bisphenol A, S, and AF in some concentrations (with p-values ranging from p ≤ 0.05 to p ≤ 0.001). Our findings confirm prior research that bisphenol A and its supposedly safer analogs exert a detrimental effect on diverse biological processes. Therefore, bisphenol A analogs should be employed with caution, particularly until a comprehensive risk assessment has been conducted. Full article
(This article belongs to the Special Issue Caenorhabditis elegans: A Model Organism for Human Health and Disease)
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10 pages, 2206 KiB  
Article
Isothiocyanate-Rich Moringa Seed Extract Activates SKN-1/Nrf2 Pathway in Caenorhabditis elegans
by Renalison Farias-Pereira, Pierre Camayoc and Ilya Raskin
Int. J. Mol. Sci. 2024, 25(20), 10917; https://doi.org/10.3390/ijms252010917 - 10 Oct 2024
Viewed by 1628
Abstract
Moringa oleifera is a tropical tree that has its leaves, fruits, and seeds used as medicine and food. A standardized hydroalcoholic moringa seed extract (MSE) contains up to 40% of an isothiocyanate (MIC-1; moringin), a phytochemical known to have antioxidant and anti-inflammatory properties. [...] Read more.
Moringa oleifera is a tropical tree that has its leaves, fruits, and seeds used as medicine and food. A standardized hydroalcoholic moringa seed extract (MSE) contains up to 40% of an isothiocyanate (MIC-1; moringin), a phytochemical known to have antioxidant and anti-inflammatory properties. Animal studies suggest that MSE may help with diseases, such as edema, colitis, obesity, and diabetes. In vitro studies have shown that MIC-1 activates the Nrf2 pathway, involved in detoxification and antioxidant pathways. To broaden the understanding of the molecular pathways regulated by MSE, we hypothesized that MSE improves the health span in Caenorhabditis elegans by activating the Nrf2 homolog (SKN-1). Our whole RNA-seq data showed that MSE at 0.1 mg/mL (100 µM MIC-1) regulated the expression of a total of 1555 genes, including genes related to C. elegans cuticle, molting cycle, and glutathione metabolism. MSE upregulated several glutathione S transferases (GST), involved in the detoxification of xenobiotics, and other SKN-1 downstream targets. MSE and MIC-1 upregulate skn-1 expression and induce SKN-1 nuclear translocation, suggesting that they activate the SKN-1/Nrf2 pathway. Moreover, the regulation of glutathione metabolism is likely dependent on the SKN-1 pathway, as the gst-4 upregulation by MSE was inhibited in skn-1 knockout mutant. However, MSE decreased survivability and delayed growth rate, while purified MIC-1 increased the lifespan of C. elegans. This study shows that MIC-1 is responsible for SKN-1/Nrf2 activation by MSE; however, components other than MIC-1 within MSE likely cause detrimental effects in C. elegans. Full article
(This article belongs to the Special Issue Caenorhabditis elegans: A Model Organism for Human Health and Disease)
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