scholarly journals Intergenerational hormesis is regulated by heritable 18S rRNA methylation

2021 ◽  
Author(s):  
Noa Liberman ◽  
Maxim V. Gerashchenko ◽  
Konstantinos Boulias ◽  
Fiona G MacWhinnie ◽  
Albert Kejun Ying ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Stress Resistance ◽  
Genetic Information ◽  
18S Rrna ◽  
Genetic Material ◽  
C Elegans ◽  
Complex Phenotypes ◽  
Extended Longevity ◽  
Heat Stress Resistance ◽  
Rrna Methylation

SummaryHeritable non-genetic information can regulate a variety of complex phenotypes. However, what specific non-genetic cues are transmitted from parents to their descendants are poorly understood. Here, we perform metabolic methyl-labelling experiments to track the heritable transmission of methylation from ancestors to their descendants in the nematode Caenorhabditis elegans. We find that methylation is transmitted to descendants in proteins, RNA, DNA and lipids. We further find that in response to parental starvation, fed naïve progeny display reduced fertility, increased heat stress resistance, and extended longevity. This intergenerational hormesis is accompanied by a heritable increase in N6’-dimethyl adenosine (m6,2A) on the 18S ribosomal RNA at adenosines 1735 and 1736. We identified the conserved DIMT-1 as the m6,2A methyltransferase in C. elegans and find that dimt-1 is required for the intergenerational hormesis phenotypes. This study provides the first labeling and tracking of heritable non-genetic material across generations and demonstrates the importance of rRNA methylation for regulating the heritable response to starvation.

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 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 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 Bacterial processing of glucose modulates C. elegans lifespan and healthspan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samuel F. Kingsley ◽  
Yonghak Seo ◽  
Calista Allen ◽  
Krishna S. Ghanta ◽  
Steven Finkel ◽  
...  
Keyword(s):  
Stress Resistance ◽  
Critical Role ◽  
Glutathione S Transferase ◽  
Negative Effects ◽  
E Coli ◽  
C Elegans ◽  
Growth Defects ◽  
Glycation End Products ◽  
Heat Stress Resistance ◽  
Dietary Sugar

AbstractIntestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a Caenorhabditis elegans-E. coli system where only the bacteria have direct contact with glucose. Our data reveal that bacterial processing of glucose results in reduced lifespan and healthspan including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. With chronic exposure to glucose, E. coli exhibits growth defects and increased advanced glycation end products. These negative effects are abrogated when the E. coli is not able to process the additional glucose and by the addition of the anti-glycation compound carnosine. Physiological changes of the host C. elegans are accompanied by dysregulation of detoxifying genes including glyoxalase, glutathione-S-transferase, and superoxide dismutase. Loss of the glutathione-S-transferase, gst-4 shortens C. elegans lifespan and blunts the animal's response to a glucose fed bacterial diet. Taken together, we reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define a critical role of detoxification genes in maintaining health during a chronic high-sugar diet.

scholarly journals N6-adenosine methylation of ribosomal RNA affects lipid oxidation and stress resistance

2020 ◽  
Vol 6 (17) ◽  
pp. eaaz4370 ◽  
Author(s):  
Noa Liberman ◽  
Zach K. O’Brown ◽  
Andrew Scott Earl ◽  
Konstantinos Boulias ◽  
Maxim V. Gerashchenko ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Stress Resistance ◽  
Dietary Supplementation ◽  
Stress Sensitivity ◽  
Stress Signaling ◽  
Omega 3 ◽  
C Elegans ◽  
Selective Translation ◽  
Specific Mrnas ◽  
Global Translation

During stress, global translation is reduced, but specific transcripts are actively translated. How stress-responsive mRNAs are selectively translated is unknown. We show that METL-5 methylates adenosine 1717 on 18S ribosomal RNA in C. elegans, enhancing selective ribosomal binding and translation of specific mRNAs. One of these mRNAs, CYP-29A3, oxidizes the omega-3 polyunsaturated fatty acid eicosapentaenoic acid to eicosanoids, key stress signaling molecules. While metl-5–deficient animals grow normally under homeostatic conditions, they are resistant to a variety of stresses. metl-5 mutant worms also show reduced bioactive lipid eicosanoids and dietary supplementation of eicosanoid products of CYP-29A3 restores stress sensitivity of metl-5 mutant worms. Thus, methylation of a specific residue of 18S rRNA by METL-5 selectively enhances translation of cyp-29A3 to increase production of eicosanoids, and blocking this pathway increases stress resistance. This study suggests that ribosome methylation can facilitate selective translation, providing another layer of regulation of the stress response.

scholarly journals Bacterial processing of glucose modulates C. elegans lifespan and healthspan

2020 ◽  
Author(s):  
Samuel F. Kingsley ◽  
Yonghak Seo ◽  
Calista Allen ◽  
Krishna S. Ghanta ◽  
Steven Finkel ◽  
...  
Keyword(s):  
Stress Resistance ◽  
Critical Role ◽  
Glutathione S Transferase ◽  
Negative Effects ◽  
E Coli ◽  
C Elegans ◽  
Growth Defects ◽  
Glycation End Products ◽  
Heat Stress Resistance ◽  
Dietary Sugar

AbstractIntestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a C. elegans-E. coli system. Our data reveal that bacterial processing of glucose, rather than direct ingestion by the animal, results in reduced lifespan and healthspan, including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. Chronic exposure of E. coli to glucose produces growth defects and increased advanced glycation end products within the E. coli. These negative effects are abrogated when the E. coli is not able to process the additional glucose and by the addition of the anti-glycation compound carnosine. Physiological changes of the host C. elegans are accompanied by dysregulation of detoxifying genes including glyoxalase, glutathione-S-transferase, and superoxide dismutase. Loss of gst-4 shortens C. elegans lifespan and blunts the animal’s response to a glucose-fed bacteria diet. Taken together, we reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define the critical role of detoxification genes in maintaining health during a chronic high-sugar diet.

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.

Phylogeny of hymenolepidids (Cestoda: Cyclophyllidea) from mammals: sequences of 18S rRNA and COI genes confirm major clades revealed by the 28S rRNA analyses

2021 ◽  
Vol 95 ◽  
Author(s):  
B. Neov ◽  
G.P. Vasileva ◽  
G. Radoslavov ◽  
P. Hristov ◽  
D.T.J. Littlewood ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
18S Rrna ◽  
Phylogenetic Analyses ◽  
The Other ◽  
Rrna Genes ◽  
Host Switching ◽  
28S Rrna ◽  
Mitochondrial Cytochrome ◽  
Rapid Radiation ◽  
18S Rrna Genes

Abstract The aim of the study is to test a hypothesis for the phylogenetic relationships among mammalian hymenolepidid tapeworms, based on partial (D1–D3) nuclear 28S ribosomal RNA (rRNA) genes, by estimating new molecular phylogenies for the group based on partial mitochondrial cytochrome c oxidase I (COI) and nuclear 18S rRNA genes, as well as a combined analysis using all three genes. New sequences of COI and 18S rRNA genes were obtained for Coronacanthus integrus, C. magnihamatus, C. omissus, C. vassilevi, Ditestolepis diaphana, Lineolepis scutigera, Spasskylepis ovaluteri, Staphylocystis tiara, S. furcata, S. uncinata, Vaucherilepis trichophorus and Neoskrjabinolepis sp. The phylogenetic analyses confirmed the major clades identified by Haukisalmi et al. (Zoologica Scripta 39: 631–641, 2010): Ditestolepis clade, Hymenolepis clade, Rodentolepis clade and Arostrilepis clade. While the Ditestolepis clade is associated with soricids, the structure of the other three clades suggests multiple evolutionary events of host switching between shrews and rodents. Two of the present analyses (18S rRNA and COI genes) show that the basal relationships of the four mammalian clades are branching at the same polytomy with several hymenolepidids from birds (both terrestrial and aquatic). This may indicate a rapid radiation of the group, with multiple events of colonizations of mammalian hosts by avian parasites.

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.

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