scholarly journals Forward genetic screen forCaenorhabditis elegansmutants with a shortened locomotor healthspan

2018 ◽  
Author(s):  
Kazuto Kawamura ◽  
Ichiro N. Maruyama
Keyword(s):  
Progressive Decline ◽  
Forward Genetic Screen ◽  
C Elegans ◽  
Short Lifespan ◽  
Elongator Complex ◽  
Age Related ◽  
Mutant Strains ◽  
Complex Protein ◽  
Locomotor Impairment ◽  
Locomotor Deficits

AbstractTwo people with the same lifespan do not necessarily have the same healthspan. One person may retain locomotor and cognitive functions until the end of life, while another person may lose them during adulthood. Unbiased searches for genes that are required to maintain locomotor capacities during adulthood may uncover key regulators of locomotor healthspan. Here, we take advantage of the relatively short lifespan of the nematodeCaenorhabditis elegansand develop a novel screening procedure to collect mutants with locomotor deficits that become apparent in adulthood. After ethyl methanesulfonate mutagenesis, we isolated fiveC. elegansmutant strains that progressively lose adult locomotor activity. In one of the mutant strains, a nonsense mutation in Elongator Complex Protein Component 2 (elpc-2)causes a progressive decline in locomotor function. Mutants and mutations identified in the present screen may provide insights into mechanisms of age-related locomotor impairment and the maintenance of locomotor healthspan.

scholarly journals LONGEVITY OVER THE COUNTER: INVESTIGATING THE EFFECTS OF COMMON DIETARY SUPPLEMENTS ON AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S102-S103
Author(s):  
Ben Blue ◽  
Elena Vayndorf ◽  
Matt Kaeberlein
Keyword(s):  
Body Wall ◽  
Video Recording ◽  
The Body ◽  
Limiting Factor ◽  
Time Of Death ◽  
Image Capture ◽  
Over The Counter ◽  
C Elegans ◽  
Short Lifespan ◽  
Age Related

Abstract C. elegans has been a workhorse within the field of aging biology for several decades due to its short lifespan, easy culturing, and robust genetic tools. However, the limiting factor in using C. elegans has been that throughput was constrained by the time and effort needed to manually check the worms for signs of life during longitudinal studies. By using the WormBot, a robotic image capture platform, we are able to successfully screen a wide array of compounds for their effects upon C. elegans lifespan. A single WormBot can monitor 144 individual experiments simultaneously and allows for accurate time of death calls. Here we present data generated with the WormBot that includes a screen of compounds from a wide array of natural and synthetic products that are often available as over-the-counter supplements. In order to better examine the effects of these widely-used compounds upon the aging process and an age-associated disease we examined longevity in a wildtype strain of C. elegans as well as an engineered strain that expresses human Aβ protein in the body wall muscle. The age-related pathogenesis of the Aβ-expressing strain is a progressive paralysis that can be halted with treatment of known effectors of Alzheimer’s disease. As such, we screened our battery of compounds with this strain to determine which compounds have a significant affect on delaying Aβ-associated paralysis. Lastly, using the WormBot’s ability to capture video recording, we examine how each compound affects mobility as animals age.

scholarly journals Odor Sensitivity as a Biomarker of Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 121-122
Author(s):  
Marjana Sarker ◽  
Scott Leiser
Keyword(s):  
Olfactory System ◽  
Healthy Adult ◽  
Model Organism ◽  
Olfactory Neurons ◽  
Adult Lifespan ◽  
C Elegans ◽  
Short Lifespan ◽  
Age Related ◽  
Odor Sensitivity ◽  
Biomarker Of Aging

Abstract Recent studies support the deterioration of the sense of smell as an important biomarker for cognitive impairment diseases, including Alzheimer’s disease. The model organism C. elegans has a well-studied olfactory system, which provides an ideal platform to measure loss of smell with aging. The goal of our project is to use the short lifespan and olfactory changes observed in nematodes to identify mechanisms to slow aging and treat age-related diseases. Our approach is to utilize worms at various times of their healthy adult lifespan and to test for their sensitivity to known attractants such as benzaldehyde. These odorants are largely detected by the main AWC olfactory neurons. It is well documented that the responsiveness of AWC decreases with age. Our paradigm is to briefly fast worms to increase motivation before testing their ability to discriminate odors. Our results show that younger worms actively move toward the attractant and show preference for specific attractants. However, older worms frequently do not respond to attractive odors and remain near the point of origin, regardless of motility. These results indicate a decreased odor response with age. Our current work focuses on identifying genes and compounds that positively affect this odor response in older animals. The resulting data can then be tested for their efficacy to improve other aspects of healthspan and potentially longevity.

scholarly journals A forward genetic screen in Drosophila implicates insulin signaling in age-related locomotor impairment

2009 ◽  
Vol 44 (8) ◽  
pp. 532-540 ◽  
Author(s):  
Melanie A. Jones ◽  
Julia Warner Gargano ◽  
Devin Rhodenizer ◽  
Ian Martin ◽  
Poonam Bhandari ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Genetic Screen ◽  
Forward Genetic Screen ◽  
Age Related ◽  
Locomotor Impairment

scholarly journals Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans

2021 ◽  
Author(s):  
Ineke Dhondt ◽  
Clara Verschuuren ◽  
Aleksandra Zečić ◽  
Tim Loier ◽  
Bart P. Braeckman ◽  
...  
Keyword(s):  
Close Association ◽  
Visual Assessment ◽  
Muscle Architecture ◽  
Biological Age ◽  
Progressive Decline ◽  
C Elegans ◽  
Age Related ◽  
Gfp Reporter ◽  
The Relationship ◽  
Microscopy Images

Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the commonalities with human muscle structure and facile visualization possibilities, C. elegans represents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens to identify modulators that mitigate age-related muscle frailty and thus improve healthspan in C. elegans.

Eugenol Elicits Prolongevity by Increasing Resistance to Oxidative Stress in C. elegans

2021 ◽  
Vol 20 ◽  
Author(s):  
Nikhat Parween ◽  
Amber Jabeen ◽  
Birendra Prasad
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Caenorhabditis Elegans ◽  
Ocimum Sanctum ◽  
Human Consumption ◽  
C Elegans ◽  
Slowing Down ◽  
Age Related ◽  
Mutant Strains ◽  
Therapeutic Compound

Aim: To analyze the efficacy of eugenol on longevity by assessing its antioxidant effect using Caenorhabditis elegans as an animal model. Background: Eugenol is a major polyphenolic component of Ocimum sanctum (Tulsi) which attributes wide pharmacological activities and can serve as a biomarker. However, the possible effect of eugenol on longevity in Caenorhabditis elegans has not been reported. Objective: The objective of this investigation was to provide first scientific based results about effect of eugenol on longevity, slowing down of paralysis in Alzheimer’s model and mechanism behind it in Caenorhabditis elegans animal model system. Results: Extract of Ocimum sanctumand eugenol increased lifespan and provided indemnity against pro-oxidants. It also significantly improved healthy ageing and slowed the progression of neurodegeneration in CL4176 Alzheimer’s model of worm by increasing survival against prooxidants and slowing down the paralysis. Longevity effect was independent of the DAF-16 as observed by using DAF-16::GFP and daf-16 null mutant strains. These results implicate eugenol as a potent therapeutic compound which may curtail ageing and age related disorders like- Alzheimer’s disease. Conclusion: The present work demonstrated eugenol as a potential anti-ageing compound which may curtail ageing, improve heath span by enhancing resistance to oxidative stress and exerts its effect independent of DAF-16 pathway. So, it can be assumed that eugenol can be beneficial to humans as well, albeit further research is necessary before declaring it for human consumption.

scholarly journals Energy Metabolism and Ageing in the Mouse: A Mini-Review

Gerontology ◽  
2017 ◽  
Vol 63 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Vian Azzu ◽  
Teresa G. Valencak
Keyword(s):  
Energy Metabolism ◽  
Metabolic Rate ◽  
Mouse Models ◽  
Model Organism ◽  
Transgenic Mouse Models ◽  
Progressive Decline ◽  
Short Lifespan ◽  
Mutant Strains ◽  
Extended Lifespan ◽  
Over Time

The mouse has rapidly become the mammalian model organism of choice in ageing research due to its relatively short lifespan, the proximity of its genome and physiology to humans, and most importantly due to its genetic pliability and the availability of mutant strains. Mouse models have provided great insights into the ageing process, which in its broadest sense is the progressive decline of body functions over time. In this mini-review, we briefly cover the historical views on the link between ageing and metabolic rate, highlight genetically modified transgenic mouse models of extended lifespan, discuss endocrine pathways linked to senescence and ageing, and then examine pathways by which caloric restriction is postulated to result in longevity.

scholarly journals Class I histone deacetylase HDA-3 is required for full maintenance of locomotor ability in Caenorhabditis elegans

2019 ◽  
Author(s):  
Kazuto Kawamura ◽  
Ichiro N. Maruyama
Keyword(s):  
Histone Deacetylase ◽  
Genetic Factors ◽  
Class I ◽  
Causative Mutation ◽  
Progressive Decline ◽  
C Elegans ◽  
Age Related ◽  
Genetic And Environmental Factors ◽  
Chromosome Ii ◽  
Locomotor Ability

ABSTRACTLocomotor ability declines with old age. A person’s capacity to maintain locomotor ability depends on genetic and environmental factors. Currently, the specific genetic factors that work to maintain locomotor ability are not well understood. Here we report the involvement of hda-3, encoding a class I histone deacetylase, as a specific genetic factor that contributes to the maintenance of locomotor ability in C. elegans. From a forward genetic approach, we identified a missense mutation in HDA-3 as the causative mutation for progressive decline in locomotor ability in one of the isolated strains. From transcriptome analysis, we found downregulated expression of two clusters of genes on Chromosome II and IV in this strain. Genes carrying CUB-like domains and genes carrying BATH domains were found on Chromosome II and IV, respectively. Knockdown of CUB-like genes, K08D8.5 and dod-17, and BATH genes, bath-1, bath-21 and bath-24 led to a progressive decline in locomotor ability. Our study identifies specific genetic factors that work to maintain locomotor ability and reveals potential targets for delaying age-related locomotor decline.

Antifungal Activity Directed Toward the Cell Wall by 2-Cyclohexylidenhydrazo- 4-Phenyl-Thiazole Against Candida albicans

2019 ◽  
Vol 19 (4) ◽  
pp. 428-438 ◽  
Author(s):  
Nívea P. de Sá ◽  
Ana P. Pôssa ◽  
Pilar Perez ◽  
Jaqueline M.S. Ferreira ◽  
Nayara C. Fonseca ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Mammalian Cells ◽  
C Elegans ◽  
Buccal Epithelial Cells ◽  
Mutant Strains ◽  
Low Toxicity ◽  
High Concentrations ◽  
Mic Value

<p>Background: The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds. </P><P> Objective: To investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2- cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans. </P><P> Methods: The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans. </P><P> Results: CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase. </P><P> Conclusion: In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans.</p>

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

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