The nematode Caenorhabditis elegans as a model for aging research

Mack, Hildegard I. D.; Heimbucher, Thomas; Murphy, Coleen T.

doi:10.1016/j.ddmod.2018.11.001

Cited by 44 publications

(43 citation statements)

References 185 publications

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“…Dead L. paracasei D3-5 feeding extends lifespan in Caenorhabditis (C.) elegans The onset of aging is associated with decline in muscle mass, and in physical and cognitive functions. Wild-type C. elegans N2 is a widely used animal model in several anti-aging screening studies (Mack et al 2019;Tissenbaum 2015b). In a previous study (Nagpal et al 2018b), we isolated six probiotic Lactobacillus strains (viz.…”

Section: Resultsmentioning

confidence: 99%

Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice

et al. 2019

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Increased inflammation associated with leaky gut is a major risk factor for morbidity and mortality in older adults; however, successful preventive and therapeutic strategies against these conditions are not available. In this study, we demonstrate that a human-origin Lactobacillus paracasei D3-5 strain (D3-5), even in the non-viable form, extends life span of Caenorhabditis elegans. In addition, feeding of heat-killed D3-5 to old mice (> 79 weeks) prevents high-fat diet-induced metabolic dysfunctions, decreases leaky gut and inflammation, and improves physical and cognitive functions. D3-5 feeding significantly increases mucin production, and proportionately, the abundance of mucin-degrading bacteria Akkermansia muciniphila also increases. Mechanistically, we show that the lipoteichoic acid (LTA), a cell wall component of D3-5, enhances mucin (Muc2) expression by modulating TLR-2/p38-MAPK/NF-kB pathway, which in turn reduces age-related leaky gut and inflammation. The findings indicate that the D3-5 and its LTA can prevent/treat age-related leaky gut and inflammation.

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Section: Resultsmentioning

confidence: 99%

Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice

et al. 2019

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“…C. elegans , as with all model organisms, has several limitations as well. For example, it lacks many tissues and organs present in humans such as the heart, kidney, liver, lungs and eyes [ 128 , 142 ]. In addition, the intestine in C. elegans is the major organ for detoxification and fat storage functions that in mammals are carried out by the liver and adipose tissue, respectively [ 143 ].…”

Section: Important Considerations For Geroprotective Drug Screeninmentioning

confidence: 99%

Phenotypic Screening in C. elegans as a Tool for the Discovery of New Geroprotective Drugs

Bulterijs

Braeckman

2020

Pharmaceuticals

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Population aging is one of the largest challenges of the 21st century. As more people live to advanced ages, the prevalence of age-related diseases and disabilities will increase placing an ever larger burden on our healthcare system. A potential solution to this conundrum is to develop treatments that prevent, delay or reduce the severity of age-related diseases by decreasing the rate of the aging process. This ambition has been accomplished in model organisms through dietary, genetic and pharmacological interventions. The pharmacological approaches hold the greatest opportunity for successful translation to the clinic. The discovery of such pharmacological interventions in aging requires high-throughput screening strategies. However, the majority of screens performed for geroprotective drugs in C. elegans so far are rather low throughput. Therefore, the development of high-throughput screening strategies is of utmost importance.

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“…The worm species Caenorhabditis elegans (C. elegans) is one of the most studied model organisms in longevity research and has signi cantly contributed to our fundamental understanding of organismal ageing [6]. C. elegans has a short lifespan of approximately 3 weeks which makes it well suited for longevity studies in contrast to long-lived mammals [6,7]. Besides its short lifespan, C. elegans displays several observable and quanti able changes with ageing in its anatomical and functional features.…”

Section: Caenorhabditis Elegans In Ageing Researchmentioning

confidence: 99%

“…Besides its short lifespan, C. elegans displays several observable and quanti able changes with ageing in its anatomical and functional features. Thus, the ageing process can be easily monitored [6,7].…”

Section: Caenorhabditis Elegans In Ageing Researchmentioning

confidence: 99%

Random forest classification for predicting lifespan-extending chemical compounds

Kapsiani

Howlin

2020

Preprint

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Ageing is a major risk factor for many conditions including cancer, cardiovascular and neurodegenerative diseases. Pharmaceutical interventions that slow down ageing and delay the onset of age-related diseases are a growing research area. The aim of this study was to build a machine learning model based on the data of the DrugAge database to predict whether a chemical compound will extend the lifespan of the worm species Caenorhabditis elegans. Five predictive models were built using the random forest algorithm with molecular fingerprints and/or molecular descriptors as features. Feature selection was achieved using variation and mutual information-based methods. The best performing classifier, built using molecular descriptors, achieved an area under the curve (AUC) score of 0.815 for classifying the compounds in the test set. The features of the model were ranked using the Gini importance measure of the random forest algorithm. The top 30 most important features included descriptors related to atom and bond counts, topological and partial charge properties. The model was applied to predict the class of compounds in an external database, consisting of 1,738 small-molecules. The chemical compounds of the screening database with a predictive probability of ≥ 0.80 for increasing the lifespan of Caenorhabditis elegans were broadly separated into (i) flavonoids, (ii) fatty acids and conjugates, and (iii) organooxygen compounds.

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The nematode Caenorhabditis elegans as a model for aging research

Cited by 44 publications

References 185 publications

Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice

Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice

Phenotypic Screening in C. elegans as a Tool for the Discovery of New Geroprotective Drugs

Random forest classification for predicting lifespan-extending chemical compounds

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