Genes Skn-1 Research Articles

Zein nanoparticles extend lifespan in C. elegans and SAMP8 mice

Empty zein nanoparticles (NP) have been shown to lower glycemia in rats by stimulating the secretion of endogenous GLP-1. This study evaluated the effect of these nanoparticles on the lifespan of two animal models: C. elegans fed with a glucose-rich diet and the senescence accelerated mouse-prone 8 (SAMP8 mice). In C. elegans, NP increased the mean lifespan of worms by 7 days (from 17.1 for control to 24.5 days). This observation was in line with the observed significant reductions of glucose and fat contents, lipofuscin accumulation, and ROS expression. Furthermore, NP supplementation led to an upregulation of the expression of daf-16 and skn-1 genes. DAF-16 (orthologue of the FOXO family) and SKN-1 (orthologue of mammalian Nrf/CNC proteins) are implicated in activating detoxification mechanisms against oxidative damage. In SAMP8, oral administration of NP also extended the mean lifespan of mice (by 28 % compared to controls), corroborating the protective effect of these nanoparticles.

Anti-aging effect of glycerophosphocholine in Steinernema kraussei 0657L.

Glycerophosphocholine (GPC) is a water-soluble small molecule found naturally in humans and foods such as milk and soybeans. It can activate the IIS pathway by regulating the expression of daf-2, ins-18 and daf-16 genes, sek-1 and skn-1 genes of MAPK pathway, sod-3, ctl-1, gst-4 and other antioxidant genes. GPC can relieve symptoms related to aging in organisms. The aim of this study was to probe the effects of GPC on the longevity and stress resistance of the entomopathogenic nematode (EPN) Steinernema kraussei 0657L strain. The results showed that the lifespan of S. kraussei 0657L was significantly prolonged by 50mM GPC treatment, which was 54.55% longer than that of the control (0mM GPC). GPC significantly inhibited reactive oxygen species (ROS) and lipofuscin accumulation, but the body size and fecundity of S. kraussei 0657L had little changed. At the same time, the longevity of S. kraussei 0657L exposed to heat shock and UV-B radiation was significantly prolonged than that with no external stress. GPC supplementation increased the activity of antioxidant enzymes and corresponding gene expression. Under treatment with 50mM GPC, the activities of superoxide dismutase and catalase were increased by 1.90- and 4.13-fold, respectively, the expression of the sod-3 and ctl-1 genes was increased by 3.60- and 0.60-fold, respectively, and harmful reactive oxygen species were removed. In addition, the expression levels of the ins-18, skn-1, sek-1 and gst-4 genes related to the insulin/IGF-1 signaling pathway were upregulated 1.04-, 1.84-, 2.21- and 1.24-fold, respectively. These results indicate that GPC is mainly involved in the lifespan regulation of S. kraussei 0657L and plays an important role in resistance to external stress by activating the insulin/IGF-1 signaling pathway and downstream PI3K/MAPK kinase, creating a new idea for improving the commercial efficacy of S. kraussei. It also laid a theoretical foundation for its further efficient development and utilization in the field of biological control.

Insight of Silkworm Pupa Oil Regulating Oxidative Stress and Lipid Metabolism in Caenorhabditis elegans.

Silkworm pupa oil (SPO) contains unsaturated fatty acids, tocopherols, and phytosterols, which can regulate serum total cholesterol or be used as an antioxidant. In this study, we investigated the impacts of SPO on the antioxidant stress and lipid metabolism of Caenorhabditis elegans. The lifespan of the C. elegans fed with different SPO concentrations was determined. The levels of endogenous reactive oxygen species (ROS) were analyzed with the fluorescent probe method. The activity of antioxidant enzymes and the content of malondialdehyde (MDA) were analyzed. The transcription level of specific mRNA was characterized with q-PCR. The survival time of the mutant strain under oxidative stress was determined by daf-2 (CB1370) mutant, sod-3 (GA186) mutant, and skn-1 (EU31) mutant. As for the lipid metabolism, the lipid accumulation was determined with an Oil-Red-O (ORO) staining. The transcription level of specific mRNA was determined by q-PCR. The results showed that the SPO feeding enhanced the activities of antioxidant enzyme by upregulating the expression of the genes skn-1, and sod-3 to decrease the production of ROS and MDA, which prolonged the life of nematodes treated with juglone. ORO staining analysis indicated the feeding of SPO decreased intestinal fat accumulation, downregulated expression of fat-5, fat-6, fat-7, and nhr-80, and upregulated age-1 and tph-1 expression. Conclusively, SPO enhanced the antioxidant capacity by regulating the skn-1 and sod-3 expression of antioxidant gene and reducing the fat accumulation by the insulin/IGF signaling pathway and nuclear hormone receptor nhr-80 signaling pathway of nematodes. This study provides new evidence for the antioxidant and lipid-lowering mechanisms of SPO in C. elegans.

Effects of Rhodiola rosea and its major compounds on insulin resistance in Caenorhabditis elegans

• Hyperglycemic insulin resistance model of C. elegans is conducted. • Major compounds are identified in Rhodiola rosea extact (EAE). • Effects of EAE on insulin resistance in C. elegans is evaluated. • EAE could activate IRS and AMPK pathways. By establishing insulin resistance model of Caenorhabditis elegans , the effects of Rhodiola rosea extract and its compounds on glucose level, insulin signal intensity, antioxidant enzymes and cell apoptosis of C. elegans were investigated in present study. The mRNA expression of DAF-2, DAF-16, AkT-1, SKN-1, AAK-2 and SOD-3 were detected by qRT-PCR. The results revealed that R. rosea extract contain salidroside, kaempferol, chlorogenic acid, kaemphenol-7- O -glucoside, caffeic acid, and quercetin, etc. At the concentration of 200 μg/mL, R. rosea extract treated C. elegans showed increased insulin signal intensity by 52.46% compared with the normal group, while, glucose content decreased by 72.13% and reactive oxygen species (ROS) level decreased by 36.84%. Compared with high glucose model group, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) increased by 10.9, 14.2 and 27.9, respectively. After R. rosea extract intervention, the expression levels of DAF-2, AkT-1, AAK-2, SKN-1 and other genes significantly increased. These results also indicated that R. rosea extract could activate insulin receptor substrate (IRS) and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) pathways to enhance insulin signaling, promote nutrient metabolism, and achieve the effect for improving insulin resistance of C. elegans .

Flavonoids from Lycium barbarum Leaves Exhibit Anti-Aging Effects through the Redox-Modulation.

Lycium barbarum leaves are a kind of vegetable, and modern nutrition studies have found that they have an anti-aging function. Our study aims to investigate the anti-aging effects of Lycium barbarum leaf flavonoid (LBLF) extracts and its underlying molecular mechanism. LBLFs were purified using D101 and polyamide resin, characterized by ultraperformance liquid chromatography coupled with mass spectrometry, and administered to hydrogen peroxide (H2O2)-treated human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. Appropriate enrichment conditions were optimized through dynamic adsorption and desorption experiments, the content of flavonoids reached 909.84 mg/g, rutin and kaempferol being the main ones. LBLFs attenuated H2O2-induced HUVEC apoptosis, decreased reactive oxygen species and malondialdehyde production levels, increased superoxide dismutase, glutathione peroxidase and catalase activities. Furthermore, pre-treatment with LBLF increased mRNA expression of erythropoietin (EPO) and heme oxygenase-1 (HO-1) via the mitogen-activated protein kinase (MAPK) signaling pathway in HUVECs. Compared with 100 µM rutin monomer, LBLF prolonged the lifespan of Caenorhabditis elegans, enhanced their mobility in middle life stages and upregulated expression of sod-2, gcs-1 and skn-1 genes, which indicated that the anti-aging effects of LBLF were due to its redox-modulation.

Scorpion Venom Heat-Resistant Synthesized Peptide Increases Stress Resistance and Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1-Like Signal Pathway.

Improving healthy life expectancy by targeting aging-related pathological changes has been the spotlight of geroscience. Scorpions have been used in traditional medicine in Asia and Africa for a long time. We have isolated heat-resistant peptides from scorpion venom of Buthusmartensii Karsch (SVHRP) and found that SVHRP can attenuate microglia activation and protect Caenorhabditis elegans (C. elegans) against β-amyloid toxicity. Based on the amino acid sequence of these peptides, scorpion venom heat–resistant synthesized peptide (SVHRSP) was prepared using polypeptide synthesis technology. In the present study, we used C. elegans as a model organism to assess the longevity-related effects and underlying molecular mechanisms of SVHRSP in vivo. The results showed that SVHRSP could prolong the lifespan of worms and significantly improve the age-related physiological functions of worms. SVHRSP increases the survival rate of larvae under oxidative and heat stress and decreases the level of reactive oxygen species and fat accumulation in vivo. Using gene-specific mutation of C. elegans, we found that SVHRSP-mediated prolongation of life depends on Daf-2, Daf-16, Skn-1, and Hsf-1 genes. These results indicate that the antiaging mechanism of SVHRSP in nematodes might be mediated by the insulin/insulin-like growth factor-1 signaling pathway. Meanwhile, SVHRSP could also up-regulate the expression of stress-inducing genes Hsp-16.2, Sod-3, Gei-7, and Ctl-1 associated with aging. In general, our study may have important implications for SVHRSP to promote healthy aging and provide strategies for research and development of drugs to treat age-related diseases.

The Modulatory Role of sti-1 in Methylmercury-Induced Toxicity in Caenorhabditis elegans.

Human exposure to the neurotoxin methylmercury (MeHg) poses a significant health risk to the development of the nervous system. The mechanisms of MeHg-induced neurotoxicity are associated with the disruption of cellular homeostasis, and include oxidative stress, loss of calcium homeostasis, and impaired protein quality control. The stress inducible protein 1 (STI-1) is involved in the regulation of protein quality control by acting as a protein cochaperone to maintain optimal protein unfolding and refolding. Here, we utilized the Caenorhabditis elegans (C. elegans) model of MeHg toxicity to characterize the role of the sti-1 gene in MeHg-induced toxicity. We showed that lifespan and developmental milestone timings were significantly altered in sti-1 knockout (KO) animals with MeHg exposure. However, knocking down sti-1 by RNAi did not result in an analogous effect for lifespan, but did still sensitize to delays in developmental milestone progression by acute MeHg, suggesting that insufficiency of sti-1 does not recapitulate all phenotypes of the null mutation. Furthermore, inhibition of ATP levels by MeHg exposure was modulated by sti-1. Considering that the skn-1/gst-4 pathway is highly involved in metal's toxicity, such pathway was also explored in our model. We showed that sti-1 mutant worms exhibited impaired capacity to upregulate the antioxidant genes skn-1/gst-4, highlighting a central role of sti-1 in modulating antioxidant response. Lastly, we showed that loss-of-function mutation in the rrf-3 gene, which encodes a putative RNA-directed RNA polymerase, has significant effect in altering MeHg-induced toxicity by potentiating the animal's detoxification system. Altogether, our novel data show an indispensable role of protein quality control in the defense against MeHg toxicity.

Activation of autophagy attenuates motor deficits and extends lifespan in a C. elegans model of ALS

Mutations in Cu/Zn–superoxide dismutase 1 (SOD1) are linked to amyotrophic lateral sclerosis (ALS). Using a line of ALS-related mutant human SOD1 (hSOD1) transgenic Caenorhabditis elegans, we determined the effects of metformin on the progression of ALS-like pathological abnormalities. We found that metformin significantly extended the lifespan, improved motor performance, and enhanced antioxidant activity of mutant worms. We further showed that metformin enhanced expression of lgg-1, daf-16, skn-1 and other genes known to regulate autophagy, longevity and oxidative stress in hSOD1 transgenic worms. Accordingly, overexpression of lgg-1 or daf-16 attenuated the aging and pathological abnormalities of mutant human SOD1 worms, while genetic deletion of lgg-1 or daf-16 abolished the beneficial effects of metformin. Collectively, we demonstrate that metformin protects against mutant SOD1-induced cytotoxicity in part through enhancement of autophagy and extends lifespan through daf-16 pathway. Our findings suggest that metformin could be further explored as a potential therapeutic agent in treating ALS.

A Potential Probiotic Lactobacillus plantarum JBC5 Improves Longevity and Healthy Aging by Modulating Antioxidative, Innate Immunity and Serotonin-Signaling Pathways in Caenorhabditis elegans.

Since the hypothesis of Dr. Elie Metchnikoff on lactobacilli-mediated healthy aging, several microbes have been reported to extend the lifespan with different features of healthy aging. However, a microbe affecting diverse features of healthy aging is of choice for broader acceptance and marketability as a next-generation probiotic. We employed Caenorhabditis elegans as a model to understand the potential of Lactobacillus plantarum JBC5 (LPJBC5), isolated from fermented food sample on longevity and healthy aging as well as their underlying mechanisms. Firstly, LPJBC5 enhanced the mean lifespan of C. elegans by 27.81% compared with control (untreated). LPBC5-induced longevity was accompanied with better aging-associated biomarkers, such as physical functions, fat, and lipofuscin accumulation. Lifespan assay on mutant worms and gene expression studies indicated that LPJBC5-mediated longevity was due to upregulation of the skinhead-1 (skn-1) gene activated through p38 MAPK signaling cascade. Secondly, the activated transcription factor SKN-1 upregulated the expression of antioxidative, thermo-tolerant, and anti-pathogenic genes. In support, LPJBC5 conferred resistance against abiotic and biotic stresses such as oxidative, heat, and pathogen. LPJBC5 upregulated the expression of intestinal tight junction protein ZOO-1 and improved gut integrity. Thirdly, LPJBC5 improved the learning and memory of worms trained on LPJBC5 compared with naive worms. The results showed upregulation of genes involved in serotonin signaling (ser-1, mod-1, and tph-1) in LPJBC5-fed worms compared with control, suggesting that serotonin-signaling was essential for LPJBC5-mediated improved cognitive function. Fourthly, LPJBC5 decreased the fat accumulation in worms by reducing the expression of genes encoding key substrates and enzymes of fat metabolism (i.e., fat-5 and fat-7). Lastly, LPJBC5 reduced the production of reactive oxygen species and improved mitochondrial function, thereby reducing apoptosis in worms. The capability of a single bacterium on pro-longevity and the features of healthy aging, including enhancement of gut integrity and cognitive functions, makes it an ideal candidate for promotion as a next-generation probiotic.

The triterpenoid ursolic acid ameliorates stress in Caenorhabditis elegans by affecting the depression-associated genes skn-1 and prdx2

IntroductionDepression is one of the leading causes of death worldwide. Lower antioxidant concentrations and increased oxidative stress levels contribute to the development of depression. Effective and tolerable medications are urgently needed. Nrf2 and PRDX2 are promising targets in the treatment of oxidative stress and, therefore, promising for the development of novel antidepressants. Ursolic acid (UA), a natural triterpenoid found in various plants is known to exert neuroprotective and antioxidant effects. Skn-1 (which corresponds to human Nrf2) and prdx2 deficient mutants of the nematode Caenorhabditis elegans are suitable models to study the effect of UA on these targets. Additionally, stress assays are used to mimic stress or depressed state. MethodsWe examined the antioxidant activity of UA in Caenorhabditis elegans wildtype and skn-1- and prdx2-deficient strains by H2DCF-DA and juglone assays as well as osmotic and heat stress assays. Additionally, we analyzed the binding of UA to human PRDX2 and Skn-1 proteins by molecular docking and microscale thermophoresis. ResultsUA exerted strong antioxidant activities. Additionally, induction of stress resistance towards osmotic and heat stress was observed. qRT-PCR revealed that UA upregulated the gene expression of skn-1 and prdx2. Molecular docking studies supported these findings. ConclusionOur findings implicate that the strong antioxidant activity of UA may exert anti-depressive effects by its interaction with the Skn-1 transcription factor, which is part of a detoxification network, and the antioxidant PRDX2 protein, which protects the organism from the detrimental effects of radical oxygen species.

Physicochemical characterization and antioxidant effects of green microalga Chlorella pyrenoidosa polysaccharide by regulation of microRNAs and gut microbiota in Caenorhabditis elegans

A novel polysaccharide from Chlorella pyrenoidosa (CPP) was separated and purified with the average molecular weight 15.8 kDa. It was composed of seven monosaccharides including mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. FT-IR and NMR spectra analysis further revealed that CPP was an acidic polysaccharide consisting of β-L-Arap-(1→, →2)-α-L-Rhap-(1→, β-D-GlcpA-(1→, →4)-α-D-GalpA-(1→, →6)-β-D-Glcp-(1→, →3)-β-D-Manp-(1→, and →3, 6)-β-D-Galp-(1→. The CPP treatment could effectively prolong lifespan of Caenorhabditis elegans under the oxidative stress conditions and inhibit the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) as well as enhancing the level of superoxide dismutase (SOD). It could up-regulate the expressions of Daf-16 and Skn-1 genes via declining miR-48-3p, miR-48-5p, and miR-51-5p translocation. Moreover, 16S rRNA sequencing revealed that the CPP-enriched Faecalibacterium, Haemophilus, Vibrio, and Shewanella were strongly correlated with SOD, MDA, apoptosis, and ROS. These results indicated that CPP may be considered as a desired ingredient on regulating the aging and oxidative diseases.

Cyanobacterial pigment protein allophycocyanin exhibits longevity and reduces Aβ-mediated paralysis in C. elegans: complicity of FOXO and NRF2ortholog DAF-16 and SKN-1.

The allophycocyanin (APC) protein purified from Phormidium sp. A09DM was investigated for its in vivo antioxidant and anti-aging potential in Caenorhabditis elegans. An increased mean lifespan of APC-treated (100μg/ml) worms (wild type) were observed from 16 ± 0.2days (control) to 20 ± 0.1days (treated). APC-treated worms also showed improved physiological marker of aging such as the rate of pharyngeal pumping and higher rate of survival against oxidative and thermal stress. Furthermore, APC was found to moderate the expression of human amyloid beta (Aβ1-42) as well as associated Aβ-induced paralysis in the transgenic C. elegans CL4176 upon increase in temperature. Furthermore, RNA interference (RNAi)-mediated studies revealed the dependence of downstream regulator daf-16, independent of stress-induced resistance gene skn-1 in the APCtreated C. elegans. In the present study, we tried to demonstrate the anti-aging activity, longevity and protective effects of APC against cellular stress in C. elegans, which can lead to the use of this biomolecule in drug development for age-related disorders.

Microplastic (1 and 5 μm) exposure disturbs lifespan and intestine function in the nematode Caenorhabditis elegans

As an emerging environmental pollutant, microplastics (MPs) are increasingly viewed as a serious health concern to terrestrial and aquatic ecosystems. However, previous toxicological studies examining MPs on freshwater and terrestrial organisms provide contradictory results, possibly due to few investigations at environmentally relevant concentrations. Here, the nematode Caenorhabditis elegans (C. elegans), a model organisms with both aquatic and terrestrial free-living forms, was employed to investigate the effects of 1 and 5 μm MPs (107–1010 particles/m2) on the intake, lifespan, defecation rhythm, defecation-related neurons and transcriptional expression of related genes (skn-1, mkk-4, pmk-1, cpr-1 and itr-1). We demonstrated that the percentage of MP-contaminated nematodes increased with increasing exposure concentrations and duration. The lifespan of nematodes in the lower concentration exposure groups (2.4 × 107 and 2.4 × 108 particles/m2) decreased more prominently than that of higher concentration groups (2.4 × 109 and 2.4 × 1010 particles/m2) after a 72-h exposure period. Concomitantly, expression of the skn-1 gene, involved in detoxification and lifespan regulation, was significantly altered at lower MP concentrations. Physiologically, the defecation rhythm after a 72-h exposure period was most strongly affected by 1 μm MPs at 2.4 × 108 particles/m2. The significant up-regulation of related genes by 1 μm MPs appears responsible for the shortened defecation interval. Results of this study identified a potential toxicity threat to C. elegans from exposure to MPs at environmentally relevant concentrations and provide novel evidence for MP risks to freshwater and terrestrial organisms.Capsule.After exposure to 1 and 5 μm MPs (107–1010 particles/m2), the lifespan of C. elegans decreased more rapidly at lower concentrations.

1,3,5,8-Tetrahydroxy-9H-xanthen-9-one exerts its antiageing effect through the regulation of stress-response genes and the MAPK signaling pathway.

The antioxidative effects of 30 xanthone derivatives (XDs) (XD-n, n = 1-30) in HepG2 cells were evaluated by the cellular antioxidant activity assay. Results showed that all XDs were antioxidants and 1,3,5,8-tetrahydroxy-9H-xanthen-9-one (XD-2) was the most active antioxidant. The all-oxygenated substituted xanthones extended the lifespan of wild-type N2 nematodes under normal culture conditionsand XD-2 was the best one. XD-2 eliminated excessive intracellular reactive oxygen species and enhanced the expression levels and activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. XD-2 inhibited the H2 O2 -increased phosphorylation levels of c-JUN N-terminal kinase, extracellular signal-regulated kinase, and p38 in HepG2 cells. In vivo, XD-2 also extended the lifespan of wild-type N2 nematodes under oxidative stress induced by paraquat, but failed in extending the lifespan of CF1038 (daf-16 deletion) and AY102 (pmk-1 deletion) mutant nematodes. It was revealed by real-time polymerase chain reaction that the genes daf-16, sir-2.1, akt-1, and age-1 were all inhibited by paraquat stimuli, while XD-2 reversed these inhibitions; in contrast, paraquat stimuli upregulated both the skn-1 and pmk-1 genes. However, treatment byXD-2 further increased the levels of both genes. These pieces ofevidence implied that XD-2 promotes longevity through endogenous signaling pathways rather than through the antioxidative activity alone. Taken all together, it may be concluded that XD-2 is a promising antiageing agent.

Leaf extract of Caesalpinia mimosoides enhances oxidative stress resistance and prolongs lifespan in Caenorhabditis elegans

BackgroundCaesalpinia mimosoides, a vegetable consumed in Thailand, has been reported to exhibit in vitro antioxidant properties. The in vivo antioxidant and anti-aging activities have not been investigated. The aim of this research was to study the antioxidant activity of C. mimosoides extracts in Caenorhabditis elegans, a widely used model organism in this context.MethodsC. elegans were treated with C. mimosoides extracts in a various concentrations. To investigate the protective effects of the extract against oxidative stress, wild-type N2 were used to determine survival rate under oxidative stress and intracellular ROS. To study underlying mechanisms, the mutant strains with GFP reporter gene including TJ356, CF1553, EU1 and LD4 were used to study DAF-16, SOD-3, SKN-1 and GST-4 gene, respectively. Lifespan and aging pigment of the worms were also investigated.ResultsA leaf extract of C. mimosoides improved resistance to oxidative stress and reduced intracellular ROS accumulation in nematodes. The antioxidant effects were mediated through the DAF-16/FOXO pathway and SOD-3 expression, whereas the expression of SKN-1 and GST-4 were not altered. The extract also prolonged lifespan and decreased aging pigments, while the body length and brood size of the worms were not affected by the extract, indicating low toxicity and excluding dietary restriction.ConclusionsThe results of this study establish the antioxidant activity of C. mimosoides extract in vivo and suggest its potential as a dietary supplement and alternative medicine to defend against oxidative stress and aging, which should be investigated in intervention studies.

Studying Oxidative Stress Caused by the Mitis Group Streptococci in Caenorhabditis elegans.

Caenorhabditis elegans (C. elegans), a free-living nematode, has emerged as an attractive model to study host-pathogen interactions. The presented protocol uses this model to determine the pathogenicity caused by the mitis group streptococci via the production of H2O2. The mitis group streptococci are an emerging threat that cause many human diseases such as bacteremia, endocarditis, and orbital cellulitis. Described here is a protocol to determine the survival of these worms in response to H2O2 produced by this group of pathogens. Using the gene skn-1 encoding for an oxidative stress response transcription factor, it is shown that this model is important for identifying host genes that are essential against streptococcal infection. Furthermore, it is shown that activation of the oxidative stress response can be monitored in the presence of these pathogens using a transgenic reporter worm strain, in which SKN-1 is fused to green fluorescent protein (GFP). These assays provide the opportunity to study the oxidative stress response to H2O2 derived by a biological source as opposed to exogenously added reactive oxygen species (ROS) sources.

Pro-oxidant and lifespan extension effects of caffeine and related methylxanthines in Caenorhabditis elegans

Caffeine and related purine alkaloids are common ingredients of many stimulating drinks. Studies have shown that lower concentrations of caffeine have a protective role in aging-related disorders. However, the associated mode of action of caffeine and its related methylxanthines is still not clear. In this study, we demonstrated that caffeine and theophylline promote longevity in Caenorhabditis elegans. Lifespan studies with the wild type, DAF-16 and SKN-1 mutant strains indicated that the methylxanthines-mediated lifespan extension in C. elegans was independent of DAF-16/FOXO and SKN-1. All the tested methylxanthines could protect C. elegans against acute oxidative stress. At early stages of life, an increase of ROS (reactive oxygen species) induced the translocation of DAF-16 and SKN-1, resulting in upregulation of several antioxidant genes, for example, sod-3p::GFP, gst-4p::GFP, gcs-1p::GFP; and downregulation of hsp-16.2p::GFP. RT-PCR corroborates the upregulation of gst-4 and skn-1 genes. The expression of DAF-16 decreased although its nuclear translocation was induced.

Toxic Effects of Bisphenol A, Propyl Paraben, and Triclosan on Caenorhabditis elegans.

Bisphenol A (BPA) is a ubiquitous plasticizer which is absorbed by ingestion and dermal contact; propyl paraben (PPB) inhibits the microbiome and extends the shelf life of many personal care products, whereas triclosan (TCS) is commonly found in antiseptics, disinfectants, or additives. In this work, Caenorhabditis elegans was used as a biological model to assess the toxic effects of BPA, PPB, and TCS. The wild type strain, Bristol N2, was used in bioassays with the endpoints of lethality, growth, and reproduction; green fluorescent protein (GFP) transgenic strains with the hsp-3, hsp-4, hsp-16.2, hsp-70, sod-1, sod-4, cyp-35A4, cyp-29A2, and skn-1 genes were evaluated for their mRNA expression through fluorescence measurement; and quick Oil Red O (q ORO) was utilized to stain lipid deposits. Lethality was concentration-dependent, while TCS and PPB showed more toxicity than BPA. BPA augmented worm length, while PPB reduced it. All toxicants moderately increased the width and the width–length ratio. BPA and PPB promoted reproduction, in contrast to TCS, which diminished it. All toxicants affected the mRNA expression of genes related to cellular stress, control of reactive oxygen species, and nuclear receptor activation. Lipid accumulation occurred in exposed worms. In conclusion, BPA, PPB, and TCS alter the physiology of growth, lipid accumulation, and reproduction in C. elegans, most likely through oxidative stress mechanisms.

VITAMIN D PROMOTES PROTEIN HOMEOSTASIS AND LONGEVITY VIA STRESS RESPONSE GENES SKN-1, IRE-1, AND XBP-1

Vitamin D has multiple roles including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitaminD, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that Vitamin D3-induced lifespan extension requires the stress response pathway genes SKN-1, IRE-1, and XBP-1. Vitamin D3 (D3) induced expression of SKN-1 target genes, but not canonical targets of IRE-1/XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels, and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.

Plant-parasitic nematodes: towards understanding molecular players in stress responses.

Background Plant–parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant–nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Scope Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1, which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. Conclusion DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches.