scholarly journals Genes implicated in Caenorhabditis elegans and human health regulate stress resistance and physical abilities in aged Caenorhabditis elegans

2021 ◽  
Vol 17 (6) ◽  
pp. 20200916
Author(s):  
Jessica Dysarz ◽  
Georg Fuellen ◽  
Steffen Möller ◽  
Walter Luyten ◽  
Christian Schmitz-Linneweber ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Bioinformatics Analyses ◽  
C Elegans ◽  
Swim Performance ◽  
Health Related ◽  
Physical Abilities ◽  
Heat Stress Resistance ◽  
Literature Curation

Recently, nine Caenorhabditis elegans genes, grouped into two pathways/clusters, were found to be implicated in healthspan in C. elegans and their homologues in humans, based on literature curation, WormBase data mining and bioinformatics analyses. Here, we further validated these genes experimentally in C. elegans . We downregulated the nine genes via RNA interference (RNAi), and their effects on physical function (locomotion in a swim assay) and on physiological function (survival after heat stress) were analysed in aged nematodes. Swim performance was negatively affected by the downregulation of acox-1.1 , pept-1 , pak-2 , gsk-3 and C25G6.3 in worms with advanced age (twelfth day of adulthood) and heat stress resistance was decreased by RNAi targeting of acox-1.1 , daf-22 , cat-4 , pig-1 , pak-2 , gsk-3 and C25G6.3 in moderately (seventh day of adulthood) or advanced aged nematodes. Only one gene, sad-1 , could not be linked to a health-related function in C. elegans with the bioassays we selected. Thus, most of the healthspan genes could be re-confirmed by health measurements in old worms.

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 Polyphenols and Metabolites Enhance Survival in Rodents and Nematodes—Impact of Mitochondria

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1886 ◽  
Author(s):  
Benjamin Dilberger ◽  
Maike Passon ◽  
Heike Asseburg ◽  
Carmina V. Silaidos ◽  
Fabian Schmitt ◽  
...  
Keyword(s):  
Heat Stress ◽  
Mitochondrial Function ◽  
Stress Resistance ◽  
High Performance ◽  
Healthy Aging ◽  
Respiratory Chain Complexes ◽  
Phenolic Metabolites ◽  
Expression Levels ◽  
C Elegans ◽  
Heat Stress Resistance

(1) Background: Polyphenols (PP) play an important role in the prevention of non-communicable diseases and may contribute to healthy aging. To investigate the molecular and cellular aspects of PP metabolites on longevity with a focus on mitochondrial function, we applied a pre-fermented mixture of polyphenols (Rechtsregulat®, RR) to rodents and nematodes. (2) Methods: The lifespans of Navar Medical Research Institute (NMRI) mice and C. elegans were recorded. The heat-stress resistance (37 °C) of C. elegans N2 was measured using nucleic staining. Respiration and membrane potential (ΔΨm) were measured in isolated mitochondria. The energetic metabolites adenosine triphosphate (ATP), lactate, and pyruvate were determined in lysates. Expression levels of longevity related genes were determined using quantitative real time polymerase chain reaction (qRT-PCR). Phenolic compounds were identified using ultra high performance liquid chromatography-diode array detection-Iontrap-multiple stage mass spectrometry (UHPLC-DAD-Iontrap-MSn). (3) Results: Several phenolic metabolites including protocatechuic acid (PCA) were identified in RR. Feeding of mice with RR resulted in a significantly increased lifespan. Heat-stress resistance (RR *** p = 0.0006; PCA **** p < 0.0001), median lifespan (NMRI: RR ** p = 0.0035; C. elegans RR * p = 0.0279; PCA **** p < 0.0001), and activity of mitochondrial respiratory chain complexes (RR *−** p = 0.0237 − 0.0052; PCA * p = 0.019 − 0.0208) of C. elegans were significantly increased after incubation with RR (10%) or PCA (780 µM). PCA significantly improved nematodes ΔΨm (* p = 0.02058) and ATP levels (* p = 0.029). RR significantly up-regulated lactate levels, indicating enhanced glycolysis. The expression levels of longevity related genes daf-16, sir-2.1, and skn-1 were significantly upregulated after PCA, and partially after RR administration. (4) Conclusion: Phenolic metabolites such as PCA have the potential to enhance health and lifespan and mitochondrial function, and thus may contribute to healthy aging.

scholarly journals Mitochondrial Oxidative Stress Impairs Energy Metabolism and Reduces Stress Resistance and Longevity of C. elegans

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Benjamin Dilberger ◽  
Stefan Baumanns ◽  
Fabian Schmitt ◽  
Tommy Schmiedl ◽  
Martin Hardt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Energy Metabolism ◽  
Mitochondrial Dysfunction ◽  
Respiratory Chain ◽  
Stress Resistance ◽  
Marker Genes ◽  
Heat Stress Resistance ◽  
Response Expression

Introduction. Mitochondria supply cellular energy and are key regulators of intrinsic cell death and consequently affect longevity. The nematode Caenorhabditis elegans is frequently used for lifespan assays. Using paraquat (PQ) as a generator of reactive oxygen species, we here describe its effects on the acceleration of aging and the associated dysfunctions at the level of mitochondria. Methods. Nematodes were incubated with various concentrations of paraquat in a heat-stress resistance assay (37°C) using nucleic staining. The most effective concentration was validated under physiological conditions, and chemotaxis was assayed. Mitochondrial membrane potential (ΔΨm) was measured using rhodamine 123, and activity of respiratory chain complexes determined using a Clark-type electrode in isolated mitochondria. Energetic metabolites in the form of pyruvate, lactate, and ATP were determined using commercial kits. Mitochondrial integrity and structure was investigated using transmission electron microscopy. Live imaging after staining with fluorescent dyes was used to measure mitochondrial and cytosolic ROS. Expression of longevity- and mitogenesis-related genes were evaluated using qRT-PCR. Results. PQ (5 mM) significantly increased ROS formation in nematodes and reduced the chemotaxis, the physiological lifespan, and the survival in assays for heat-stress resistance. The number of fragmented mitochondria significantly increased. The ∆Ψm, the activities of complexes I-IV of the mitochondrial respiratory chain, and the levels of pyruvate and lactate were significantly reduced, whereas ATP production was not affected. Transcript levels of genetic marker genes, atfs-1, atp-2, skn-1, and sir-2.1, were significantly upregulated after PQ incubation, which implicates a close connection between mitochondrial dysfunction and oxidative stress response. Expression levels of aak-2 and daf-16 were unchanged. Conclusion. Using paraquat as a stressor, we here describe the association of oxidative stress, restricted energy metabolism, and reduced stress resistance and longevity in the nematode Caenorhabditis elegans making it a readily accessible in vivo model for mitochondrial dysfunction.

Heat stress resistance effect of flavonoids from Penthorum chinense Pursh on Caenorhabditis elegans

2019 ◽  
Vol 15 (63) ◽  
pp. 514
Author(s):  
Chunbang Ding ◽  
Shiling Feng ◽  
Liang Fu ◽  
Yujie Wang ◽  
Handong Wang ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Penthorum Chinense Pursh ◽  
Heat Stress Resistance ◽  
Penthorum Chinense

scholarly journals IMPACT OF PHENOLIC ACIDS ON THE ENERGY METABOLISM AND LONGEVITY IN C. ELEGANS

2020 ◽  
Author(s):  
Benjamin Dilberger ◽  
Selina Weppler ◽  
Gunter P Eckert
Keyword(s):  
Heat Stress ◽  
Energy Metabolism ◽  
Phenolic Acids ◽  
Stress Resistance ◽  
Vanillic Acid ◽  
Preventive Strategy ◽  
C Elegans ◽  
Age Related ◽  
Heat Stress Resistance ◽  
Diabetes And Obesity

AbstractIntroductionAging represents one of the major risk factors for metabolic diseases, such as diabetes and obesity, or neurodegeneration. Polyphenols and its metabolites, especially simple phenolic acids, have gained more and more attention as a preventive strategy for age-related, non-communicable diseases, due to their hormetic potential. Using the nematode Caenorhabditis elegans (C. elegans) we investigate the effect of protocatechuic, gallic and vanillic acid to improve mitochondrial function and health associated parameters as a preventive measure.MethodsLifespan, heat-stress resistance and chemotaxis of C. elegans strain PX627, as a specific model for aging, were assessed in 2-day and 10-day old nematodes. Mitochondrial membrane potential (ΔΨm) and ATP generation of young and aged nematodes were measured. mRNA expression levels of longevity and energy metabolism-related genes were determined using qRT-PCR.ResultsAll phenolic acids were able to significantly increase the nematodes lifespan, heat-stress resistance and chemotaxis at micromolar concentrations. While ΔΨm was only affected by age, vanillic acid significantly decreased ATP concentrations in aged nematodes. Genetic analysis revealed increased glycolytic activity mediated through vanillic acid, suggesting improved thermogenesis.ConclusionWhile life- and health-span parameters are positively affected by the investigated phenolic acids, the concentrations applied were unable to impact mitochondrial performance, suggesting hormesis. In contrast to the other phenolic acids, vanillic acid showed potential in regulating glucose homeostasis, making it a prime candidate for future diabetes and obesity focused approaches.

Streblus asper Lour. exerts MAPK and SKN-1 mediated anti-aging, anti-photoaging activities and imparts neuroprotection by ameliorating Aβ in Caenorhabditis elegans

2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Vital Role ◽  
Transgenic Strain ◽  
Wild Type ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Streblus Asper

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.

scholarly journals Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1161
Author(s):  
Yuqing Huang ◽  
Mark G. Sterken ◽  
Koen van Zwet ◽  
Lisa van Sluijs ◽  
Gorben P. Pijlman ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Intracellular Pathogen ◽  
Potential Candidate ◽  
Molecular Responses ◽  
C Elegans ◽  
Pathogen Response ◽  
Orsay Virus ◽  
Natural Virus

The nematode Caenorhabditis elegans has been a versatile model for understanding the molecular responses to abiotic stress and pathogens. In particular, the response to heat stress and virus infection has been studied in detail. The Orsay virus (OrV) is a natural virus of C. elegans and infection leads to intracellular infection and proteostatic stress, which activates the intracellular pathogen response (IPR). IPR related gene expression is regulated by the genes pals-22 and pals-25, which also control thermotolerance and immunity against other natural pathogens. So far, we have a limited understanding of the molecular responses upon the combined exposure to heat stress and virus infection. We test the hypothesis that the response of C. elegans to OrV infection and heat stress are co-regulated and may affect each other. We conducted a combined heat-stress-virus infection assay and found that after applying heat stress, the susceptibility of C. elegans to OrV was decreased. This difference was found across different wild types of C. elegans. Transcriptome analysis revealed a list of potential candidate genes associated with heat stress and OrV infection. Subsequent mutant screens suggest that pals-22 provides a link between viral response and heat stress, leading to enhanced OrV tolerance of C. elegans after heat stress.

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