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Cell Biosci,
2016]
The generation of mutants and transgenes are indispensible for biomedical research. In the nematode Caenorhabditis elegans, a series of methods have been developed to introduce genome modifications, including random mutagenesis by chemical reagents, ionizing radiation and transposon insertion. In addition, foreign DNA can be integrated into the genome through microparticle bombardment approach or by irradiation of animals carrying microinjected extrachromosomal arrays. Recent research has revolutionized the genome engineering technologies by using customized DNA nucleases to manipulate particular genes and genomic sequences. Many streamlined editing strategies are developed to simplify the experimental procedure and minimize the cost. In this review, we will summarize the recent progress of the site-specific genome editing methods in C. elegans, including the Cre/LoxP, FLP/FRT, MosTIC system, zinc-finger nucleases (ZFNs), transcriptional activator-like nucleases (TALENs), and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease. Particularly, the recent studies of CRISPR/Cas9-mediated genome editing method in C. elegans will be emphatically discussed.
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Chem Cent J,
2015]
Age-associated neurodegenerative disorders such as Alzheimer's disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential.
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Phytomedicine,
2024]
BACKGROUND: Aging is the primary risk factor of most chronic diseases in humans, including cardiovascular diseases, osteoporosis and neurodegenerative diseases, which extensively damage the quality of life for elderly individuals. Aging is a multifaceted process with numerous factors affecting it. Efficient model organisms are essential for the research and development of anti-aging agents, particularly when investigating pharmacological mechanisms are needed. PURPOSE: This review discusses the application of Caenorhabditis elegans for studying aging and its related signaling pathways, and presents an overview of studies exploring the mechanism and screening of anti-aging agents in C. elegans. Additionally, the review summarizes related clinical trials of anti-aging agents to inspire the development of new medications. METHOD: Literature was searched, analyzed, and collected using PubMed, Web of Science, and Science Direct. The search terms used were "anti-aging", "medicinal plants", "synthetic compounds", "C. elegans", "signal pathway", etc. Several combinations of these keywords were used. Studies conducted in C. elegans or humans were included. Articles were excluded, if they were on studies conducted in silico or in vitro or could not offer effective data. RESULTS: Four compounds mainly derived through synthesis (metformin, rapamycin, nicotinamide mononucleotide, alpha-ketoglutarate) and four active ingredients chiefly obtained from plants (resveratrol, quercetin, Astragalus polysaccharide, ginsenosides) are introduced emphatically. These compounds and active ingredients exhibit potential anti-aging effects in preclinical and clinical studies. The screening of these anti-aging agents and the investigation of their pharmacological mechanisms can benefit from the use of C. elegans. CONCLUSION: Medicinal plants provide valuable resource for the treatment of diseases. A wide source of raw materials for the particular plant medicinal compounds having anti-aging effects meet diverse pharmaceutical requirements, such as immunomodulatory, anti-inflammation and alleviating oxidative stress. C. elegans possesses advantages in scientific research including short life cycle, small size, easy maintenance, genetic tractability and conserved biological processes related to aging. C. elegans can be used for the efficient and rapid evaluation of compounds with the potential to slow down aging.
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Bioessays,
1990]
The signal for sex determination in the nematode Caenorhabditis elegans is the ratio between the number of X chromosomes and the number of sets of autosomes (the X/A ratio). Animals with an X/A ratio of 0.67 (a triploid with two X chromosomes) or less are males. Animals with an X/A ratio of 0.75 or more are hermaphrodites. Thus, diploid males have one X chromosome and diploid hermaphrodites have two X chromosomes. However, the difference in X-chromosome number between the sexes is not reflected in general levels of X-linked gene expression because of the phenomenon of dosage compensation. In dosage compensation, X-linked gene expression appears to be 'turned down' in 2X animals to the 1X level of expression. An intriguing and unexplained finding is that mutations and X-chromosome duplications that elevate X-linked gene expression also feminize triploid males. One way that this relationship between sex determination and X-linked gene expression may be operating is discussed.
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Trends Genet,
2000]
The nematode Caenorhabditis elegans counts its X chromosomes to determine sex and to activate the process of dosage compensation, which ensures that males (XO) and hermaphrodites (XX) express equal levels of most X-chromosome products. The number of X chromosomes is communicated by a set of X-linked genes called X-signal elements, which repress the master sex-determination switch gene
xol-1 via two distinct, dose-dependent molecular mechanisms in XX embryos. X-chromosome gene dosage is compensated by a specialized protein complex that includes evolutionarily conserved components of mitotic and meiotic machinery. This complex assembles on both X chromosomes of hermaphrodites to repress transcription by half. The recruitment of chromosome segregation proteins to the new task of regulating X-chromosome-wide gene expression points to the evolutionary origin of nematode dosage compensation.
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J Genomics,
2015]
In many animals, males have one X and females have two X chromosomes. The difference in X chromosome dosage between the two sexes is compensated by mechanisms that regulate X chromosome transcription. Recent advances in genomic techniques have provided new insights into the molecular mechanisms of X chromosome dosage compensation. In this review, I summarize our current understanding of dosage imbalance in general, and then review the molecular mechanisms of X chromosome dosage compensation with an emphasis on the parallels and differences between the three well-studied model systems, M. musculus, D. melanogaster and C. elegans.
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Trends Cell Biol,
2000]
Animals that have XX females and XY or XO males have differing doses of X-linked genes in each sex. Overcoming this is the most immediate and vital aspect of sexual differentiation. A number of systems that accurately compensate for sex-chromosome dosage have evolved independently: silencing a single X chromosome in female mammals, downregulating both X chromosomes in hermaphrodite Caenorhabditis elegans and upregulating the X chromosome in male Drosophila all equalize X-linked gene expression. Each organism uses a largely non-overlapping set of molecules to achieve the same outcome: 1X = 2X.
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Science,
1995]
In many species, females possess two X chromosomes and males have one X chromosome. This difference is critical for the initial determination of sex. However, the X encodes many functions required equally in males and females; thus, X chromosome expression must be adjusted to compensate for the difference in dosage between the sexes. Distinct dosage compensation mechanisms have evolved in different species. A common theme in the Drosophila melanogaster and Caenorhabditis elegans systems is that a subtle alteration of chromatin structure may impose this modest, but vital adjustment of the X chromosome
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Curr Opin Genet Dev,
1998]
Dosage compensation ensures that individuals with a single X chromosome have the same amount of most X-linked gene products as those with two. In Drosophila, this equalization is achieved by a two-fold enhancement of the level of transcription of the X in males (XY) relative to each X chromosome in females (XX). In Caenorhabditis, equalization of X-linked gene products between hermaphrodites (XX) and males (XO) is achieved by decreasing the activity of genes in the former. These two different solutions to the common problem of unequal dosage of X-linked genes in different sexes provide invaluable paradigms for the study of gene regulation at the level of chromatin remodeling.
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Curr Opin Genet Dev,
2022]
Gametogenesis produces the only cell type within a metazoan that contributes both genetic and epigenetic information to the offspring. Extensive epigenetic dynamics are required to express or repress gene expression in a precise spatiotemporal manner. On the other hand, early embryos must be extensively reprogrammed as they begin a new life cycle, involving intergenerational epigenetic inheritance. Seminal work in both Drosophila and C. elegans has elucidated the role of various regulators of epigenetic inheritance, including (1) histones, (2) histone-modifying enzymes, and (3) small RNA-dependent epigenetic regulation in the maintenance of germline identity. This review highlights recent discoveries of epigenetic regulation during the stepwise changes of transcription and chromatin structure that takes place during germline stem cell self-renewal, maintenance of germline identity, and intergenerational epigenetic inheritance. Findings from these two species provide precedence and opportunity to extend relevant studies to vertebrates.