Expression Of Daf-16 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.

Astragalin from Thesium chinense: A Novel Anti-Aging and Antioxidant Agent Targeting IGFR/CD38/Sirtuins.

Astragalin (AG), a typical flavonoid found in Thesium chinense Turcz (T. chinense), is abundant in various edible plants and possesses high nutritional value, as well as antioxidant and antibacterial effects. In this study, we initially predicted the mechanism of action of AG with two anti-aging and antioxidant-related protein targets (CD38 and IGFR) by molecular docking and molecular dynamics simulation techniques. Subsequently, we examined the anti-aging effects of AG in Caenorhabditis elegans (C. elegans), the antioxidant effects in zebrafish, and verified the related molecular mechanisms. In C. elegans, AG synergistically extended the lifespan of C. elegans by up-regulating the expression of daf-16 through inhibiting the expression of daf-2/IGFR and also activating the AMPK and MAPK pathways to up-regulate the expression of sir-2.1, sir-2.4, and skn-1. In oxidatively damaged zebrafish embryos, AG demonstrated a synergistic effect in augmenting the resistance of zebrafish embryos to oxidative stress by up-regulating the expression levels of SIRT1 and SIRT6 within the zebrafish embryos system via the suppression of CD38 enzymatic activity and then inhibiting the expression of IGFR through high levels of SIRT6. These findings highlight the antioxidant and anti-aging properties of AG and indicate its potential application as a supplementary ingredient in aquaculture for enhancing fish health and growth.

Lactobacillus paracasei subsp. paracasei 2004 improves health and lifespan in Caenorhabditis elegans

Recent research has highlighted the importance of the gut microbiome in regulating aging, and probiotics are interventions that can promote gut health. In this study, we surveyed several novel lactic acid bacteria to examine their beneficial effect on organismal health and lifespan in C. elegans. We found that animals fed some lactic acid bacteria, including L. acidophilus 1244 and L. paracasei subsp. paracasei 2004, grew healthy. Supplementation with the lactic acid bacterial strains L. acidophilus 1244 or L. paracasei subsp. paracasei 2004 significantly improved health, including food consumption, motility, and resistance to oxidative stressor, hydrogen peroxide. Our RNA-seq analysis showed that supplementation with L. paracasei subsp. paracasei 2004 significantly increased the expression of daf-16, a C. elegans FoxO homolog, as well as genes related to the stress response. Furthermore, daf-16 deletion inhibited the longevity effect of L. paracasei subsp. paracasei 2004 supplementation. Our results suggest that L. paracasei subsp. paracasei 2004 improves health and lifespan in a DAF-16-dependent manner.

Lactobacillus fermentum WC2020 increased the longevity of Caenorhabditis elegans via JNK-mediated antioxidant pathway.

Lactobacillus fermentum can exert antiaging effects, but their roles are strain-specific, and little is known about the molecular mechanisms in some strains. This study investigated the antiaging effects of L. fermentum WC2020 (WC2020) isolated from Chinese fermented pickles and the underlying mechanism of the action in Caenorhabditis elegans. WC2020 enhanced the mean lifespan of L1-stage and L4-stage worms by 22.67% and 12.42%, respectively, compared with Escherichia coli OP50 (OP50), a standard food source for C. elegans. WC2020-induced longevity was accompanied by an increase in body length and mitochondrial transmembrane potential and a reduction in lipid accumulation and the production of reactive oxygen species and malondialdehyde. Moreover, WC2020 increased the production of glutathione, superoxide dismutases, and catalases and altered the transcripts of many phenotype-related genes. Furthermore, WC2020-fed jnk-1 rather than akt-2 or pmk-1 loss-of-function mutants showed similar lifespans to OP50-fed worms. Correspondingly, WC2020 significantly upregulated the expression of jnk-1 rather than genes involved in insulin-like, p38 MAPK, bate-catenin, or TGF-beta pathway. Moreover, the increase in body length, mitochondrial transmembrane potential, and antioxidant capability and the decrease in lipid accumulation induced by WC2020 were not observed in jnk-1 mutants. Additionally, WC2020 increased the expression of daf-16 and the proportion of daf-16::GFP in the nucleus, and increased lifespan disappeared in WC2020-fed daf-16 loss-of-function mutants. In conclusion, WC2020 activated the JNK/DAF-16 pathway to improve mitochondria function, reduce oxidative stress, and then extend the longevity of nematodes, suggesting WC2020 could be a potential probiotic targeting JNK-mediated antioxidant pathway for antiaging in food supplements and bioprocessing. PRACTICAL APPLICATION: Aging has a profound impact on the global economy and human health and could be delayed by specific diets and nutrient resources. This study demonstrated that Lactobacillus fermentum WC2020 could be a potential probiotic strain used in food to promote longevity and health via the JNK-mediated antioxidant pathway.

Intestinal Targeted Nanogel with Broad-Spectrum Autonomous ROS Scavenging Performance for Enhancing the Bioactivity of trans-Resveratrol.

To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging. A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release. Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1. This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.

Anti-aging activities of Rehmannia glutinosa Libosch. crude polysaccharide in Caenorhabditis elegans based on gut microbiota and metabonomic analysis

Aging is a degenerative progress, accompanied by oxidative damage, metabolic disorders and intestinal flora imbalance. Natural macromolecular polysaccharides have shown excellent anti-aging and antioxidant properties, while maintaining metabolic and intestinal homeostasis. The molecular weight, monosaccharide composition, infrared spectrum and other chemical structure information of four Rehmannia glutinosa polysaccharides (RG50, RG70, RG90, RGB) were determined, and their free radical scavenging ability was assessed. Molecular weight and monosaccharide composition analysis exhibited that RG50 (2–72 kDa), RG70 (3.2–37 kDa), RG70 (3–42 kDa), and RGB (3.1–180 kDa) were heteropolysaccharide with significant different monosaccharide species and molar ratios. We found that RG70 had the best antioxidant activity in vitro and RG70 could enhance the antioxidant enzyme system of Caenorhabditis elegans, diminished lipofuscin and reactive oxygen species levels, up-regulate the expression of daf-16, skn-1 and their downstream genes, and down-regulate the expression of age-1. Metabolomics results showed that RG70 mainly influenced glycine, serine and threonine metabolism and citric acid cycle. 16S rRNA sequencing showed that RG70 significantly up-regulated the abundance of Lachnospiraceae_NK4B4_group, which were positively correlated with amino acid metabolism and energy cycling. These results suggest that RG70 may delay aging by enhancing antioxidant effects, affecting probiotics and regulating key metabolic pathways.

Antioxidant Peptides Derived from Millet Bran Promote Longevity and Stress Resistance in Caenorhabditis elegans.

Millet bran as a by-product of millet grain processing remains a reservoir of active substances. In this study, functional millet bran peptides (MBPE) were obtained from bran proteins after alcalase hydrolysis and ultrafiltration. The activity of MBPE was assessed in vitro and in the model organism Caenorhabditis elegans (C. elegans). In vitro, compared to unhydrolyzed proteins, MBPE significantly enhanced the 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate (ABTS) and hydroxyl radicals scavenging activity, and the scavenging rate of MBPE with 15,000 U/g alcalase reached 42.79 ± 0.31%, 61.38 ± 0.41 and 45.69 ± 0.84%, respectively. In C. elegans, MBPE at 12.5µg/mL significantly prolonged the lifespan by reducing lipid oxidation, oxidative stress, and lipofuscin levels. Furthermore, MBPE increased the activities of the antioxidant enzymes. Genetic analyses showed that MBPE-mediated longevity was due to a significant increase in the expression of daf-16 and skn-1, which are also involved in xenobiotic and oxidative stress responses. In conclusion, this study found that MBPE had antioxidant and life-prolonging effects, which are important for the development and utilization of millet bran proteins as resources of active ingredients.

Paeoniflorin mitigates high glucose-induced lifespan reduction by inhibiting insulin signaling in Caenorhabditis elegans.

In organisms, high glucose can cause several aspects of toxicity, including the lifespan reduction. Paeoniflorin is the major component of Paeoniaceae plants. Nevertheless, the possible effect of paeoniflorin to suppress high glucose toxicity in reducing lifespan and underlying mechanism are largely unclear. Thus, in this study, we examined the possible effect of paeoniflorin in suppressing high glucose (50mM)-induced lifespan reduction and the underlying mechanism in Caenorhabditis elegans. Administration with 16-64mg/L paeoniflorin could prolong the lifespan in glucose treated nematodes. Accompanied with this beneficial effect, in glucose treated nematodes, expressions of daf-2 encoding insulin receptor and its downstream kinase genes (age-1, akt-1, and akt-2) were decreased and expression of daf-16 encoding FOXO transcriptional factor was increased by 16-64mg/L paeoniflorin administration. Meanwhile, the effect of paeoniflorin in extending lifespan in glucose treated nematodes was enhanced by RNAi of daf-2, age-1, akt-1, and akt-2 and inhibited by RNAi of daf-16. In glucose treated nematodes followed by paeoniflorin administration, the increased lifespan caused by daf-2 RNAi could be suppressed by RNAi of daf-16, suggesting that DAF-2 acted upstream of DAF-16 to regulate pharmacological effect of paeoniflorin. Moreover, in glucose treated nematodes followed by paeoniflorin administration, expression of sod-3 encoding mitochondrial Mn-SOD was inhibited by daf-16 RNAi, and the effect of paeoniflorin in extending lifespan in glucose treated nematodes could be suppressed by sod-3 RNAi. Molecular docking analysis indicated the binding potential of paeoniflorin with DAF-2, AGE-1, AKT-1, and AKT-2. Therefore, our results demonstrated the beneficial effect of paeoniflorin administration in inhibiting glucose-induced lifespan reduction by suppressing signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16-SOD-3 in insulin signaling pathway.

Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis elegans via DAF-16 mediated pathway

BACKGROUND: Hylocereus undatus is a traditional medicinal plant known for its medicinal, nutritional and commercial uses. OBJECTIVE: To address the anti-aging and neuroprotective efficacies of fruit peel extracts of H. undatus using Caenorhabditis elegans model. METHODS: C. elegans (wild-type (N2), transgenic and mutant strains) were treated with H. undatus and monitored for lifespan and neuroprotection through physiological assays, fluorescence microscopy and qPCR analysis. LC-MS/MS analysis was performed to identify the phytochemicals present in the extract. Molecular docking studies were employed to identify the interaction mode of selected phytochemicals with Aβ, DAF-16 and SKN-1. RESULTS: The extract was able to extend the lifespan of C. elegans (N2), extend the lifespan and reduce paralysis of Aβ transgenic strains CL2006 and CL4176, suggesting its anti-aging and neuroprotective potential. The LC-MS/MS analysis revealed the presence of phytochemicals including homostachydrine, betaine, syringic acid, typhaneoside, rutin, and behenic acid. The extract could activate antioxidant mechanism, through SKN-1, which was evident in qPCR and transgenic strain LG333. These effects were mediated through DAF-16 pathway as the extract was able to upregulate the expression of daf-16 in N2, increase the nuclear localization of daf-16 in transgenic strain TJ356, and not able to significantly alter the lifespan of both DAF-2 and DAF-16 mutants, CB1370 and CF1038 respectively. Finally, in molecular docking approach, typhaneoside and rutin showed better binding affinity with SKN-1 and DAF-16 when compared to resveratrol and similar binding affinity with Aβ when compared to donepezil. CONCLUSION: Taken together, this study indicates that H. undatus activates anti-aging and neuroprotection via DAF-16 mediated pathway.

Protective effects of pumpkin polysaccharide hydrolysates on oxidative stress injury and its potential mechanism — Antioxidant mechanism of pumpkin polysaccharide hydrolysates

Pumpkin polysaccharides (PPe) exhibit multiple bioactive properties, including the ability to reduce blood sugar and lipids. Our prior investigation discovered that hydrolysates (PPe-s) derived from PPe demonstrated stronger antioxidant capabilities than PPe. The objective of the current study was to explore the potential mechanism of PPe-s, utilizing Caenorhabditis elegans and MIN6 cells as models. The results of this investigation revealed that PPe-s exhibited strong scavenging ability towards ABTS+ and OH·in vitro. Additionally, PPe-s extended the lifespan of C. elegans under hydrogen peroxide stress (p < 0.05) by upregulating the mRNA expression of daf-16, sod-1, sod-3, and skn-1 (all >1.43-fold, p < 0.05). Furthermore, PPe-s enhanced the proliferation activity of MIN6 cells, induced by alloxan, increased insulin secretion and cAMP levels, and excreted intracellular excessive Ca2+ in a concentration-dependent manner. Our study demonstrated that PPe-s upregulated the expression levels of antioxidative-related genes and augmented the antioxidant defense system.

Insights into the Oxidative Stress Alleviation Potential of Enzymatically Prepared Dendrobium officinale Polysaccharides.

(1) Background: The extraction parameters can dramatically alter the extraction rate and biological activity of polysaccharides. (2) Methods: Here, an enzyme-assisted extraction (EAE) was employed to extract D. officinale polysaccharides (DOPs), and its optimal extraction conditions were established by single-factor and Box-Behnken design (BBD) experiments. Further, on the basis of in vitro antioxidant capacity, the paraquat (PQ)-induced oxidative stress of Caenorhabditis elegans (C. elegans) was chosen as a research model to explore the antioxidant activity of DOPs. (3) Results: The results showed that the extraction yield of DOPs reached 48.66% ± 1.04% under the optimal condition. In vitro experiments had shown that DOPs have considerable ABTS+ radical scavenging capacity (EC50 = 7.27 mg/mL), hydroxyl radical scavenging capacity (EC50 = 1.61 mg/mL), and metal chelating power (EC50 = 8.31 mg/mL). Furthermore, in vivo experiments indicated that DOPs (0.25 mg/mL) significantly prolonged the lifespan, increased antioxidant enzyme activity, and upregulated the expression of daf-16 (>5.6-fold), skn-1 (>5.2-fold), and sir-2.1 (>2.3-fold) of C. elegans. (4) Conclusions: DOPs can be efficiently extracted by EAE and are effective in the reduction of oxidative stress levels in C. elegans.

Knockdown of phosphatases of regenerating liver-1 prolongs the lifespan of Caenorhabditis elegans via activating DAF-16/FOXO.

Phosphatases of regenerating liver (PRLs) are dual-specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans (C. elegans). Structurally, this phosphatase in C. elegans, named PRL-1, consisted of a conserved signature sequence WPD loop and a single C(X)5 R domain. Besides, by Western blot, immunohistochemistry and immunofluorescence staining, PRL-1 was proved to mainly express in larval stages and express in intestinal tissues. Afterward, by feeding-based RNA-interference method, knockdown of prl-1 prolonged the lifespan of C. elegans but also improved their healthspan, such as locomotion, pharyngeal pumping frequency, and defecation interval time. Furthermore, the above effects of prl-1 appeared to be taken without acting on germline signaling, diet restriction pathway, insulin/insulin-like growth factor 1 signaling pathway, and SIR-2.1 but through a DAF-16-dependent pathway. Moreover, knockdown of prl-1 induced the nuclear translocation of DAF-16, and upregulated the expression of daf-16, sod-3, mtl-1, and ctl-2. Finally, suppression of prl-1 also reduced the ROS. In conclusion, suppression of prl-1 enhanced the lifespan and survival quality of C. elegans, which provides a theoretical basis for the pathogenesis of PRLs in related human diseases.

Forsythiaside B inhibits cerebral ischemia/reperfusion-induced oxidative stress injury in mice via the AMPK/DAF-16/FOXO3 pathway

To study the protective effect of forsythiaside B (FB) against cerebral oxidative stress injury induced by cerebral ischemia/reperfusion (I/R) in mice and explore the underlying mechanism. Ninety C57BL/6 mice were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) model group, and low-, medium and highdose (10, 20, and 40 mg/kg, respectively) FB groups. The expression levels of MDA, ROS, PCO, 8-OHdG, SOD, GSTα4, CAT and GPx in the brain tissue of the mice were detected using commercial kits, and those of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 were detected with Western blotting. Compound C (CC), an AMPK inhibitor, was used to verify the role of the AMPK pathway in mediating the therapeutic effect of FB. In another 36 C57BL/6 mice randomized into 4 sham-operated group, MCAO model group, FB (40 mg/kg) treatment group, FB+CC (10 mg/kg) treatment group, TTC staining was used to examine the volume of cerebral infarcts, and the levels of ROS and SOD in the brain were detected; the changes in the protein expressions of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 in the brain tissue were detected using Western blotting. In mice with cerebral IR injury, treatment with FB significantly reduced the levels of ROS, MDA, PCO and 8-OHdG, increased the activities of antioxidant enzymes SOD, GSTα4, CAT and GPx, and enhanced phosphorylation of AMPK and FOXO3 and DAF-16 protein expression in the brain tissue (P < 0.01). Compared with FB treatment alone, the combined treatment with FB and CC significantly reduced phosphorylation of AMPK and FOXO3, lowered expression of DAF-16 and SOD activity, and increased cerebral infarction volume and ROS level in the brain tissue of the mice (P < 0.01). FB inhibits oxidative stress injury caused by cerebral I/R in mice possibly by enhancing AMPK phosphorylation, promoting the downstream DAF-16 protein expression and FOXO3 phosphorylation, increasing the expression of antioxidant enzymes, and reducing ROS level in the brain tissue.

7,10,13,16-Docosatetraenoic acid impairs neurobehavioral development by increasing reactive oxidative species production in Caenorhabditis elegans

AimsTo investigate human breast milk (HBM) lipids that may adversely affect infant neurodevelopment. Main methodsWe performed multivariate analyses that combined lipidomics and psychologic Bayley-III scales to identify which HBM lipids are involved in regulating infant neurodevelopment. We observed a significant moderate negative correlation between 7,10,13,16-docosatetraenoic acid (omega-6, C22H36O2, the common name adrenic acid, AdA) and adaptive behavioral development. We further studied the effects of AdA on neurodevelopment by using Caenorhabditis elegans (C. elegans) as a model. Worms from larval stages L1 to L4 were supplemented with AdA at 5 nominal concentrations (0 μM [control], 0.1 μM, 1 μM, 10 μM, and 100 μM) and subjected to behavioral and mechanistic analyses. Key findingsSupplementation with AdA from larval stages L1 to L4 impaired neurobehavioral development, such as locomotive behaviors, foraging ability, chemotaxis behavior, and aggregation behavior. Furthermore, AdA upregulated the production of intracellular reactive oxygen species. AdA-induced oxidative stress blocked serotonin synthesis and serotoninergic neuron activity and inhibited expression of daf-16 and the daf-16–regulated genes mtl-1, mtl-2, sod-1, and sod-3, resulting in attenuation of the lifespan in C. elegans. SignificanceOur study reveals that AdA is a harmful HBM lipid that may have adverse effects on infant adaptive behavioral development. We believe this information may be critical for AdA administration guidance in children's health care.

Lonicera japonica polysaccharides improve longevity and fitness of Caenorhabditis elegans by activating DAF-16

Polysaccharide is one of the main active ingredients in Lonicera japonica Thunb. (L. japonica). In this study, we examined the anti-aging activities of L.japonica polysaccharides (LJPs) and further explored the mechanisms. Polysaccharides from L.japonica including the crude LJP (CLJP) and the purified fraction (LJP-2-1) were characterized. The molecular weights of CLJP and LJP-2-1 were 1450 kDa and 1280 kDa, respectively. Meanwhile, CLJP was mainly composed of galacturonic acid (23.57 %), galactose (23.45 %) and arabinose (23.45 %). LJP-2-1 was mainly composed of galacturonic acid (51.25 %) and arabinose (22.89 %). In Caenorhabditis elegans (C. elegans), LJPs maximally prolonged mean lifespan by 13.97 %, promoted fitness with increased motility by 40.92 % and pharyngeal pumping by 25.72 %, and decreased lipofuscin accumulation by 38.9 % with intact body length and fecundity. Moreover, CLJP extended the mean lifespan of nematodes under oxidative and heat stress by 16.76 % and 14.05 % respectively by activating stress-related genes and the antioxidant system. Further, CLJP required DAF-16 to prolong the lifespan of nematodes. CLJP upregulated the expression of daf-16 and its targeted downstream genes, including sod-3, gst-4 and hsp-16.2. Moreover, nuclear accumulation of DAF-16 was promoted upon CLJP treatment. Together, our data uncover the role of LJPs in extending lifespan and healthspan through DAF-16.

The anti-aging activity of Lycium barbarum polysaccharide extracted by yeast fermentation: In vivo and in vitro studies

Lycium barbarum polysaccharide (LBP) is an important active substance in Lycium barbarum. In this study, LBP was extracted by the hot water method and yeast fermentation method to obtain products called LBP-W and LBP-Y, respectively. Both LBPs have a strong ability to scavenge DPPH, hydroxyl, and superoxide anion free radicals and have a total antioxidant capacity. Both LBPs prolong the lifespan of C. elegans under normal conditions, oxidative stress and heat stress and do not affect fertility, LBPs could prolong the lifespan of C. elegans by upregulating the expression of daf-16, sod-3 and hsp-16.2 genes, and LBP-Y is more efficacious. The molecular weight of the LBPs was characterized by gel permeation chromatography (GPC), and the results showed that LBP-Y is smaller and more uniform than LBP-W. The skin penetration experiment showed that the absorption effect of LBP-Y is better than that of LBP-W. These lines of evidence suggest that the yeast fermentation extraction of LBP produces better antioxidant and anti-aging effects than those obtained with the traditional hot water extraction, which is more suitable for obtaining raw materials with anti-aging functions that can potentially be used in the food and cosmetic industries.

Sweet tea (Rubus Suavissmus S. Lee) polysaccharides promote the longevity of Caenorhabditis elegans through autophagy-dependent insulin and mitochondrial pathways

The fine structure of sweet tea polysaccharide (STP-60a) has been characterized. However, the biological activity of STP-60a has not been extensively explored. This study aims to evaluate the anti-aging activity of STP-60a using Caenorhabditis elegans (C. elegans) as a model and to investigate the underlying molecular mechanism. 400 μg/mL of STP-60a increased the mean lifespan of C. elegans by 22.88%, reduced the lipofuscin content by 33.01%, and improved the survival rate under heat stress and oxidative stress by 32.33% and 27.63%, respectively. Further research in lifespan-related mutants revealed that STP-60a exerted anti-aging effects mainly through insulin and mitochondrial signaling pathways. Through qRT-PCR and microscopic imaging of transgenic nematodes, we found that 400 μg/mL of STP-60a increased the expression of daf-16, skn-1, and hsf-1 downstream of the insulin pathway by 1.68-fold, 1.88-fold, and 1.03-fold, respectively, and promoted the accumulation of daf-16 and skn-1 in the nucleus. STP-60a also significantly regulated the function of the mitochondrial respiratory chain and unfolded protein recovery system. Furthermore, STP-60a activated the autophagy level in C. elegans, and the mutation of daf-2 or clk-1 inhibited the upregulation of autophagy genes by STP-60a, suggesting that autophagy acted as an effector of the insulin and mitochondrial pathways during STP-60a antiaging.

Phytochemical Composition and Anti-Aging Activity of Butanol Extract of Hedyotis diffusa in Caenorhabditis elegans.

Hedyotis diffusa Willd. (H. diffusa), a kind of traditional Chinese medicine, has been evaluated to potential display antioxidant and anti-aging effects in vitro experiments. In this work, we investigated the effects on lifespan and stress resistance of the butanol extract from H. diffusa (NHD) in vivo using a Caenorhabditis elegans (C. elegans) model. The phytochemicals of NHD were identified by UPLC-ESI-qTOF-MS/MS method. NHD-treated wild-type N2 worms showed an increase in survival time under both normal and stress conditions. Meanwhile, NHD promoted the healthspan of nematodes by stimulating growth and development, reducing the deposition of age pigment, increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase dismutase (GSH-Px), and decreasing the level of ROS without impairing fertility. Moreover, the upregulating of the expression of daf-16, gst-4, sod-3, hsp12.6 genes and the downregulating of the expression of daf-2 were involved in the NHD-mediated lifespan extension. Finally, the increasing of the expression of GST-4::GFP in CL2166 transgenic nematodes and the life-span-extending activity of NHD was completely abolished in daf-2 and daf-16 mutants further revealed that the potential roles for these genes in NHD-induced longevity in C. elegans. Collectively, our findings suggest that NHD may have an active effect in healthy aging and age-related diseases.

Sevoflurane Preconditioning Increases Stress Resistance via IMB-2/DAF-16 in Caenorhabditis Elegans.

Sevoflurane preconditioning has been proved to possess therapeutic effects on stress. However, the mechanism by which sevoflurane preconditioning protects against stress remains unclear. In this study, an acute model of heat stress in C.eleans was established. We investigated the dose-response of sevoflurane exposure on coordinated movement in C.elegans and time course for protection against heat stress of sevoflurane preconditioning to determine the optimal concentration and time point in the following experiments. EC99 of sevoflurane is 1.7% (1.3EC50) and sevoflurane preconditioning exerts the maximal protection at 6 hours after incubation, and these 2 parameters were used in our following experiments. We found that sevoflurane preconditioning increased DAF-16 nuclear translocation and enhanced the expression of DAF-16 during heat stress in N2 strain of C.elegans. DAF-16 mutation abolished the sevoflurane preconditioning-induced protection for heat stress. Furthermore, suppression of IMB-2 by RNAi prevented the upregulation of DAF-16 and enhancement of stress resistance caused by sevoflurane preconditioning. Overall, this work reveals that sevoflurane preconditioning increases the expression of DAF-16 via IMB-2 to enhance the stress resistance of C.elegans.

Lysine-glucose Maillard reaction products promote longevity and stress tolerance in Caenorhabditis elegans via the insulin/IGF-1 signaling pathway

• Maillard reaction products from lysine and glucose (LG MRPs) showed superoxide radicals scavenging activity. • LG MRPs prolonged the lifespan of C. elegans and increased their stress tolerance. • Intracellular ROS and fat accumulation were decreased by LG MRPs. • Alterations in the insulin/IGF-1 signaling pathway by LG MRPs would correlate with the longevity. The Maillard reaction is associated with the development of distinct flavors and colors during food processing and cooking. This reaction generates numerous chemical compounds, including antioxidants. Caenorhabditis elegans is a model organism for studying aging; its lifespan is prolonged by antioxidants. In this study, we investigated the effects of lysine-glucose Maillard reaction products (LG MRPs) on C. elegans lifespan. Our results showed that LG MRPs prolonged the lifespan in a dose-dependent (0.001–0.1 M) and improved the reduction of age-related movements. Reactive oxygen species and fat accumulation were decreased upon treatment with LG MRPs. LG MRPs treatment also improved oxidative and heat stress tolerance. Furthermore, mRNA expression of daf-16 which relates to the longevity and its target genes ( sod-3 , ctl-1 , hsp-12.6, and hsp-16.2 ) was increased. These results suggest that LG MRPs might contribute to longevity via the insulin/insulin-like growth factor signaling pathway in C. elegans .