scholarly journals Ferulic Acid Supplementation Increases Lifespan and Stress Resistance via Insulin/IGF-1 Signaling Pathway in C. elegans

2021 ◽  
Vol 22 (8) ◽  
pp. 4279
Author(s):  
Hui Li ◽  
Xiaoxuan Yu ◽  
Fanwei Meng ◽  
Zhenyu Zhao ◽  
Shuwen Guan ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Signaling Pathway ◽  
Underlying Mechanism ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Lifespan Extension ◽  
Rna Seq ◽  
E Coli ◽  
C Elegans ◽  
Mitochondrial Signaling

Ferulic acid (FA) is a naturally-occurring well-known potent antioxidant and free radical scavenger. FA supplementation is an effective strategy to delay aging, but the underlying mechanism remains unknown. In the present study, we examined the effects of FA on lifespan extension and its mechanism of FA in Caenorhabditis elegans (C. elegans). Results suggested that FA increased the lifespan of C. elegans, rather than altering the growth of E. coli OP50. Meanwhile, FA promoted the healthspan of C. elegans by improving locomotion and reducing fat accumulation and polyQ aggregation. FA increased the resistance to heat and oxidative stress through reducing ROS. The upregulating of the expression of the hlh-30, skn-1, and hsf-1 were involved in the FA-mediated lifespan extension. Furthermore, FA treatment had no impact on the lifespan of daf-2, hlh-30, skn-1, and hsf-1 mutants, confirming that insulin/IGF-1 signaling pathway and multiple longevity mechanisms were associated with the longevity mechanism of FA. We further found that mitochondrial signaling pathway was modulation involved in FA-mediated lifespan extension. With the results from RNA-seq results and mutants lifespan assay. These findings contribute to our knowledge of the lifespan extension and underlying mechanism of action of FA in C. elegans.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals Trilobatin, a Component from Lithocarpus polystachyrus Rehd., Increases Longevity in C. elegans Through Activating SKN1/SIRT3/DAF16 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Na Li ◽  
Xi Li ◽  
Yan-Ling Shi ◽  
Jian-Mei Gao ◽  
Yu-Qi He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Fluorescence Intensity ◽  
Body Movement ◽  
Redox Homeostasis ◽  
Underlying Mechanism ◽  
Enhancing Effect ◽  
C Elegans ◽  
Beneficial Effects ◽  
Oxidative Effects ◽  
Effective Component

Trilobatin (TLB) is an effective component from Lithocarpus polystachyrus Rehd. Our previous study revealed that TLB protected against oxidative injury in neuronal cells by AMPK/Nrf2/SIRT3 signaling pathway. However, whether TLB can delay aging remains still a mystery. Therefore, the present study was designed to investigate the possible longevity-enhancing effect of TLB, and further to explore its underlying mechanism in Caenorhabditis elegans (C. elegans). The results showed that TLB exerted beneficial effects on C. elegans, as evidenced by survival rate, body movement assay and pharynx-pumping assay. Furthermore, TLB not only significantly decreased ROS and MDA levels, but also increased anti-oxidant enzyme activities including CAT and SOD, as well as its subtypes SOD2 andSOD3, but not affect SOD1 activity, as evidenced by heat and oxidative stress resistance assays. Whereas, the anti-oxidative effects of TLB were almost abolished in SKN1, Sir2.3, and DAF16 mutant C. elegans. Moreover, TLB augmented the fluorescence intensity of DAF16: GFP, SKN1:GFP, GST4:GFP mutants, indicating that TLB increased the contents of SKN1, SIRT3 and DAF16 due to fluorescence intensity of these mutants, which were indicative of these proteins. In addition, TLB markedly increased the protein expressions of SKN1, SIRT3 and DAF16 as evidenced by ELISA assay. However, its longevity-enhancing effect were abolished in DAF16, Sir2.3, SKN1, SOD2, SOD3, and GST4 mutant C. elegans than those of non-TLB treated controls. In conclusion, TLB effectively prolongs lifespan of C. elegans, through regulating redox homeostasis, which is, at least partially, mediated by SKN1/SIRT3/DAF16 signaling pathway.

scholarly journals Integrative Systems Biology Analysis Elucidates Mastitis Disease Underlying Functional Modules in Dairy Cattle

2021 ◽  
Vol 12 ◽  
Author(s):  
Nooshin Ghahramani ◽  
Jalil Shodja ◽  
Seyed Abbas Rafat ◽  
Bahman Panahi ◽  
Karim Hasanpur
Keyword(s):  
Machine Learning ◽  
Systems Biology ◽  
Dairy Cattle ◽  
Candidate Genes ◽  
Signaling Pathway ◽  
Machine Learning Algorithms ◽  
Functional Modules ◽  
Rna Seq ◽  
Hub Genes ◽  
E Coli

Background: Mastitis is the most prevalent disease in dairy cattle and one of the most significant bovine pathologies affecting milk production, animal health, and reproduction. In addition, mastitis is the most common, expensive, and contagious infection in the dairy industry.Methods: A meta-analysis of microarray and RNA-seq data was conducted to identify candidate genes and functional modules associated with mastitis disease. The results were then applied to systems biology analysis via weighted gene coexpression network analysis (WGCNA), Gene Ontology, enrichment analysis for the Kyoto Encyclopedia of Genes and Genomes (KEGG), and modeling using machine-learning algorithms.Results: Microarray and RNA-seq datasets were generated for 2,089 and 2,794 meta-genes, respectively. Between microarray and RNA-seq datasets, a total of 360 meta-genes were found that were significantly enriched as “peroxisome,” “NOD-like receptor signaling pathway,” “IL-17 signaling pathway,” and “TNF signaling pathway” KEGG pathways. The turquoise module (n = 214 genes) and the brown module (n = 57 genes) were identified as critical functional modules associated with mastitis through WGCNA. PRDX5, RAB5C, ACTN4, SLC25A16, MAPK6, CD53, NCKAP1L, ARHGEF2, COL9A1, and PTPRC genes were detected as hub genes in identified functional modules. Finally, using attribute weighting and machine-learning methods, hub genes that are sufficiently informative in Escherichia coli mastitis were used to optimize predictive models. The constructed model proposed the optimal approach for the meta-genes and validated several high-ranked genes as biomarkers for E. coli mastitis using the decision tree (DT) method.Conclusion: The candidate genes and pathways proposed in this study may shed new light on the underlying molecular mechanisms of mastitis disease and suggest new approaches for diagnosing and treating E. coli mastitis in dairy cattle.

scholarly journals Ginsenoside Prolongs the Lifespan of C. elegans via Lipid Metabolism and Activating the Stress Response Signaling Pathway

2021 ◽  
Vol 22 (18) ◽  
pp. 9668
Author(s):  
Xiaoxuan Yu ◽  
Hui Li ◽  
Dongfa Lin ◽  
Weizhuo Guo ◽  
Zhihao Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Panax Ginseng ◽  
Underlying Mechanism ◽  
Rna Seq ◽  
Ginsenoside Re ◽  
Ginsenoside Rd ◽  
C Elegans ◽  
Kegg Pathway Analysis ◽  
And Oxidative Stress ◽  
Insight Into

Panax ginseng is a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides from Panax ginseng, on the lifespan of Caenorhabditis elegans (C. elegans). We found that TG extended the lifespan of C. elegans and reduced lipofuscin accumulation. Moreover, TG increased the survival of C. elegans in response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression of nrh-80, daf-12, daf-16, hsf-1 and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan of daf-16 and hsf-1 mutants, highlighting their role in the antiaging effects of TG in C. elegans. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg1, Rg2 and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan of C. elegans to levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside in C. elegans.

scholarly journals Volatile Composition and Biological Activity of Jordanian Commercial Samples of R. coriaria L. Fruits

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5691
Author(s):  
Rajashri R. Naik ◽  
Ashok K. Shakya ◽  
Benedetta Ferri ◽  
Ghaleb A. Oriquat ◽  
Luisa Pistelli ◽  
...  
Keyword(s):  
Essential Oils ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Local Market ◽  
Main Constituent ◽  
Agricultural Field ◽  
Main Compound ◽  
E Coli ◽  
Oxygenated Monoterpenes ◽  
Two Samples

The present paper reports the GC-HS-SPME analysis of volatile emission and GC-MS analysis of chemical composition of essential oil of R. coriaria fruits of eight different samples of R. coriaria L. fruits (“sumac” folk name), collected from Jordanian agricultural field and the local market. The analyses show an important variability among the Sumac samples probably due to the origin, cultivation, harvesting period, drying, and conservation of the plant material. The main class of component present in all samples was monoterpenes (43.1 to 72.9%), except for one sample which evidenced a high percentage of sesquiterpene hydrocarbons (38.5%). The oxygenated monoterpenes provided a contribution to total class of monoterpenes ranging from 10.1 to 24.3%. A few samples were rich in monoterpene hydrocarbons. Regarding the single components present in all the volatile emissions, β-caryophyllene was the main compound in most of the analyzed samples, varying from 34.6% to 7.9%. Only two samples were characterized by α-pinene as the main constituent (42.2 and 40.8% respectively). Essential oils were collected using hydro-distillation method. Furfural was the main constituent in almost all the analyzed EOs (4.9 to 48.1%), except in one of them, where β-caryophyllene was the most abundant one. β-caryophyllene ranged from 1.2 to 10.6%. Oxygenated monoterpenes like carvone and carvacrol ranged from 3.2–9.1% and 1.0–7.7% respectively. Cembrene was present in good amount in EO samples EO-2 to EO-8. The antioxidant capacities of the fruit essential oils from R. coriaria were assessed using spectrophotometry to measure free radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and inhibition of β-carotene bleaching (BCB). The essential oils from the fruits of the different samples of R. coriaria exhibited the MIC value ranging from 32.8 to 131.25 µg/mL against S. aureus ATCC 6538 and 131.25 to 262.5 µg/mL against E. coli ATCC 8739. The MIC values of ciprofloxacin were 0.59 and 2.34 µg/mL against S. aureus ATCC 6538 and E. coli ATCC 8739, respectively.

scholarly journals H3K9me1/2 methylation limits the lifespan of C. elegans

2021 ◽  
Author(s):  
Shouhong Guang ◽  
Meng Huang ◽  
Minjie Hong ◽  
Chengming Zhu ◽  
Di Chen ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Underlying Mechanism ◽  
Lifespan Extension ◽  
Mrna Levels ◽  
C Elegans ◽  
Histone 3 ◽  
Stem Cell Pluripotency ◽  
Receptor Mutant

Histone methylation plays crucial roles in the development, gene regulation and maintenance of stem cell pluripotency in mammals. Recent work shows that histone methylation is associated with aging, yet the underlying mechanism remains unclear. In this work, we identified a class of histone 3 lysine 9 mono-/dimethyltransferase genes (met-2, set-6, set-19, set-20, set-21, set-32 and set-33), mutations in which induce synergistic lifespan extension in the long-lived DAF-2 (IGF-1 receptor) mutant in C. elegans. These histone methyltransferase plus daf-2 double mutants not only exhibited an average lifespan nearly three times that of wild-type animals and a maximal lifespan of approximately 100 days, but also significantly increased resistance to oxidative and heat stress. Synergistic lifespan extension depends on the transcription factor DAF-16 (FOXO). mRNA-seq experiments revealed that the mRNA levels of class I DAF-16 target genes, which are activated by DAF-16, were further elevated in the double mutants. Among these genes, F35E8.7, nhr-62, sod-3, asm-2 and Y39G8B.7 are required for the lifespan extension of the daf-2;set-21 double mutant. In addition, treating daf-2 animals with the H3K9me1/2 methyltransferase G9a inhibitor also extends lifespan and increases stress resistance. Therefore, investigation of DAF-2 and H3K9me1/2 methyltransferase deficiency-mediated synergistic longevity will contribute to a better understanding of the molecular mechanisms of aging and therapeutic applications.

scholarly journals Hydroxycoumarin Grafted with Hydrazine: Synthesis, Structure Elucidation and Assessment of Antioxidant and Antibacterial Characteristics

2020 ◽  
Vol 11 (3) ◽  
pp. 10393-10401
Keyword(s):  
Chemical Structure ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
E Coli ◽  
Ir And Nmr Spectroscopy ◽  
Diffusion Technique ◽  
Staphyloccocus Aureus ◽  
Natural Organic Compound ◽  
Ft Ir ◽  
High Inhibition

4-Hydroxycoumarin, as a natural organic compound, was structurally grafted onto a benzaldehyde by hydrazine. The chemical structure of grafted macromolecule was confirmed by FT-IR and NMR spectroscopy. The antibacterial activity of the synthesized grafted macromolecule against Staphyloccocus aureus, E. coli, Proteus vulgaris, Pseudomonas, and Klebsiella pneumoniae was assessed using a disc diffusion technique. The antioxidant activity of the grafted macromolecule was also highlighted using the superoxide-radical technique. The grafted macromolecule has high inhibition activity against all tested bacteria. The grafted macromolecule was a much more effective free radical scavenger than vitamin C.

Iron-generated hydroxyl radicals kill retinal cells in vivo: effect of ferulic acid

2008 ◽  
Vol 27 (4) ◽  
pp. 327-339 ◽  
Author(s):  
HM Chao ◽  
YH Chen ◽  
JH Liu ◽  
SM Lee ◽  
FL Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ferulic Acid ◽  
Calcium Influx ◽  
Glutamate Release ◽  
Iron Particle ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Photoreceptor Outer Segments ◽  
Wave Reduction

Siderosis bulbi is vision threatening. An investigation into its mechanisms and management is crucial. Experimental siderosis was established by intravitreous administration of an iron particle (chronic) or FeSO4 (acute). After siderosis, there was a significant dose-responsive reduction in eletroretinogram (a/b-wave) amplitude, and an increase in •OH level, greater when caused by 24 mM FeSO4 than that by 8 mM FeSO4. Furthermore, the FeSO4-induced oxidative stress was significantly blunted by 100 μM ferulic acid (FA). Siderosis also resulted in an excessive glutamate release, increased [Ca++]i, and enhanced superoxide dismutase immunoreactivity. The latter finding was consistent with the Western blot result. Obvious disorganization including loss of photoreceptor outer segments and cholinergic amacrines together with a wide-spreading ferric distribution across the retina was present, which were related to the eletro-retinographic and pathologic dysfunctions. Furthermore, b-wave reduction and amacrine damage were respectively, significantly, dose-dependently, and clearly ameliorated by FA. Thus, siderosis stimulates oxidative stress, and possibly, subsequent excitotoxicity, and calcium influx, which explains why the retina is impaired electro-physiologically and pathologically. Importantly, FA protects iron toxicity perhaps by acting as a free radical scavenger. This provides an approach to the study and treatment of the iron-related disorders such as retained intraocular iron and Alzheimer disease.

scholarly journals Early Exposure is Necessary for the Lifespan Extension Effects of Cocoa in C. elegans

2021 ◽  
Vol 14 ◽  
pp. 117863882110294
Author(s):  
Mihiri Munasinghe ◽  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Deniz Heydarian ◽  
Markandeya Jois
Keyword(s):  
Lifespan Extension ◽  
Early Exposure ◽  
Mechanistic Studies ◽  
Wild Type ◽  
Survival Curves ◽  
E Coli ◽  
C Elegans ◽  
Larval Stages ◽  
Mutant Strains ◽  
Type C

Background: We previously showed that cocoa, a rich source of polyphenols improved the age-associated health and extended the lifespan in C. elegans when supplemented starting from L1 stage. Aim: In this study, we aimed to find out the effects of timing of cocoa exposure on longevity improving effects and the mechanisms and pathways involved in lifespan extension in C. elegans. Methods: The standard E. coli OP50 diet of wild type C. elegans was supplemented with cocoa powder starting from different larval stages (L1, L2, L3, and L4) till the death, from L1 to adult day 1 and from adult day 1 till the death. For mechanistic studies, different mutant strains of C. elegans were supplemented with cocoa starting from L1 stage till the death. Survival curves were plotted, and mean lifespan was reported. Results: Cocoa exposure starting from L1 stage till the death and till adult day 1 significantly extended the lifespan of worms. However, cocoa supplementation at other larval stages as well as at adulthood could not extend the lifespan, instead the lifespan was significantly reduced. Cocoa could not extend the lifespan of daf-16, daf-2, sir-2.1, and clk-1 mutants. Conclusion: Early-start supplementation is essential for cocoa-mediated lifespan extension which is dependent on insulin/IGF-1 signaling pathway and mitochondrial respiration.

scholarly journals Tianma Formula Alleviates Dementia via ACER2-Mediated Sphingolipid Signaling Pathway Involving Aβ

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Haochang Lin ◽  
Sha Wu ◽  
Zhiying Weng ◽  
Hongyan Wang ◽  
Rui Shi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Sphingolipid Metabolism ◽  
Network Pharmacology ◽  
Rna Seq ◽  
C Elegans ◽  
Metabolism Pathway

Objective. To reveal the molecular mechanism of the antagonistic effect of traditional Chinese medicine Tianma formula (TF) on dementia including vascular dementia (VaD) and Alzheimer’s disease (AD) and to provide a scientific basis for the study of traditional Chinese medicine for prevention and treatment of dementia. Method. The TF was derived from the concerted application of traditional Chinese medicine. We detected the pharmacological effect of TF in VaD rats. The molecular mechanism of TF was examined by APP/PS1 mice in vivo, Caenorhabditis elegans (C. elegans) in vitro, ELISA, pathological assay via HE staining, and transcriptome. Based on RNA-seq analysis in VaD rats, the differentially expressed genes (DEGs) were identified and then verified by quantitative PCR (qPCR) and ELISA. The molecular mechanisms of TF on dementia were further confirmed by network pharmacology and molecular docking finally. Results. The Morris water maze showed that TF could improve the cognitive memory function of the VaD rats. The ELISA and histological analysis suggested that TF could protect the hippocampus via reducing tau and IL-6 levels and increasing SYN expression. Meanwhile, it could protect the neurological function by alleviating Aβ deposition in APP/PS1 mice and C. elegans. In the RNA-seq analysis, 3 sphingolipid metabolism pathway-related genes, ADORA3, FCER1G, and ACER2, and another 5 nerve-related genes in 45 key DEGs were identified, so it indicated that the protection mechanism of TF was mainly associated with the sphingolipid metabolism pathway. In the qPCR assay, compared with the model group, the mRNA expressions of the 8 genes mentioned above were upregulated, and these results were consistent with RNA-seq. The protein and mRNA levels of ACER2 were also upregulated. Also, the results of network pharmacology analysis and molecular docking were consistent with those of RNA-seq analysis. Conclusion. TF alleviates dementia by reducing Aβ deposition via the ACER2-mediated sphingolipid signaling pathway.

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