Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice

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.

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

Biology Letters ◽

10.1098/rsbl.2020.0916 ◽

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.

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Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9

10.1101/2021.09.19.460995 ◽

2021 ◽

Author(s):

Keting Bao ◽

Jiali Feng ◽

Wenwen Liu ◽

Zhifan Mao ◽

Tianyue Sun ◽

...

Keyword(s):

Oxidative Stress ◽

Animal Model ◽

Caenorhabditis Elegans ◽

Stress Resistance ◽

Lifespan Extension ◽

Aging Effects ◽

Hypertonic Stress ◽

C Elegans ◽

Promising Application ◽

Application Prospects

While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.

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Stress resistance and lifespan extension of Caenorhabditis elegans enhanced by peptides from mussel (Mytilus edulis) protein hydrolyzate

Food & Function ◽

10.1039/c8fo00021b ◽

2018 ◽

Vol 9 (6) ◽

pp. 3313-3320 ◽

Cited By ~ 7

Author(s):

Yue Zhou ◽

Qinggang Xu ◽

Xinghua Zhou ◽

Shuang Song ◽

Beiwei Zhu

Keyword(s):

Caenorhabditis Elegans ◽

Mrna Expression ◽

Mytilus Edulis ◽

Stress Resistance ◽

Lifespan Extension ◽

Protein Hydrolyzate ◽

Lipofuscin Accumulation ◽

C Elegans

Mussel (Mytilus edulis) peptides increased stress resistance and reduced endogenous ROS level and lipofuscin accumulation of C. elegans. Mussel peptides could contribute to healthspan extension of C. elegans through regulating the mRNA expression of daf-2 and daf-16.

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

Current Aging Science ◽

10.2174/1874609813999210104203614 ◽

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.

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

Nutrition and Healthy Aging ◽

10.3233/nha-210121 ◽

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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Piceatannol, a Natural Stilbene, Extends the Lifespan of Caenorhabditis elegans Under Fasting Through Inhibition of Lipolysis

Current Developments in Nutrition ◽

10.1093/cdn/nzaa040_038 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 38-38

Author(s):

Jang Miran ◽

Zhang Yuan ◽

Bai Juan ◽

Jun-Bae An ◽

Park Yeonhwa ◽

...

Keyword(s):

Lipid Metabolism ◽

Caenorhabditis Elegans ◽

Negative Energy ◽

Hormone Sensitive Lipase ◽

Pcr Analysis ◽

Lifespan Extension ◽

Mrna Levels ◽

Free Glycerol ◽

C Elegans ◽

Glycerol Level

Abstract Objectives Lipolysis is the catabolic process that hydrolyzes triglyceride (TG) to free fatty acids (FFAs) and glycerol under negative energy balance such as fasting. In adipocytes, adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase play key roles in a series of TG hydrolysis reactions in mammals. However, overly activated adipose lipolysis is believed to contribute to link between obesity and systemic inflammation and oxidative stress. We previously demonstrated that piceatannol (PIC), a natural resveratrol analogue, inhibits adipogenesis in cultured adipocytes and lipogenesis in Caenorhabditis elegans. Furthermore, we showed that PIC extends the lifespan of C. elegans via the insulin/IGF-1 signaling. However, the effects of PIC on lipid metabolism during fasting state is unknown. Methods We conducted Oil-Red-O assay, Enzyme assay (TG and Free glycerol contents), PCR analysis and lifespan assay. Results In this study, we demonstrated that PIC-treated C. elegans exhibited suppressed lipolysis under fasting as judged by increased lipid accumulation and TG levels with decreased free glycerol level. Consistent with these findings, PIC treatment resulted in decreased mRNA levels of genes involved lipolysis such as atgl-1, hosl-1 and aak-2 in fasted C. elegans. Also, PIC treatment augmented fasting-induced lifespan of C. elegans by an increased daf-16 gene expression. However, such effect was abolished when atgl-1, aak-2, and daf-16 mutants were treated with PIC. In addition, we also found that autophagy is required for PIC-induced lifespan in C. elegans during fasting since autophagy inhibitor treatments and autophagy gene deficient worms resulted in blunting the lifespan extension effect of PIC. Conclusions Collectively, our results indicate that PIC contributes to lifespan extension in C. elegans during fasting possibly through regulating lipolysis- and/or autophagy-dependent lipid metabolism. Funding Sources 1. The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2019R1A2C1086146) and (2019R1A6A3A03033878) 2. The Rural Development Administration of the Republic of Korea.

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Effects of Orange Extracts on Longevity, Healthspan, and Stress Resistance in Caenorhabditis elegans

Molecules ◽

10.3390/molecules25020351 ◽

2020 ◽

Vol 25 (2) ◽

pp. 351 ◽

Cited By ~ 4

Author(s):

Jing Wang ◽

Na Deng ◽

Hong Wang ◽

Tong Li ◽

Ling Chen ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Stress Resistance ◽

Survival Rates ◽

Intracellular Reactive Oxygen Species ◽

Ultraviolet B ◽

Oxygen Species ◽

Aging Effects ◽

C Elegans ◽

Anti Cancer ◽

The Mean

Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on lifespan and stress resistance. The results indicated that orange extracts dose-dependently increased the mean lifespan of C. elegans by 10.5%, 18.0%, and 26.2% at the concentrations of 100, 200, and 400 mg/mL, respectively. Meanwhile, orange extracts promoted the healthspan by improving motility, and decreasing the accumulation of age pigment and intracellular reactive oxygen species (ROS) levels without damaging fertility. The survival rates of orange extract-fed worms were obviously higher than those of untreated worms against thermal and ultraviolet-B (UV-B) stress. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly enhanced while malondialdehyde (MDA) contents were diminished. Further investigation revealed that worms supplemented with orange extracts resulted in upregulated levels of genes, including daf-16, sod-3, gst-4, sek-1, and skn-1, and the downregulation of age-1 expression. These findings revealed that orange extracts have potential anti-aging effects through extending the lifespan, enhancing stress resistance, and promoting the healthspan.

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SUMO promotes longevity and maintains mitochondrial homeostasis during ageing in Caenorhabditis elegans

Scientific Reports ◽

10.1038/s41598-020-72637-9 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Andrea Princz ◽

Federico Pelisch ◽

Nektarios Tavernarakis

Keyword(s):

Caenorhabditis Elegans ◽

Posttranslational Modifications ◽

Stress Resistance ◽

Important Determinant ◽

Mitochondrial Dynamics ◽

C Elegans ◽

Mitochondrial Homeostasis ◽

Somatic Tissues ◽

Transcription Regulators ◽

Influence Gene Expression

Abstract The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors. In the nematode Caenorhabditis elegans, the transcription regulators DAF-16/FOXO and SKN-1/Nrf function to promote longevity under conditions of low insulin/IGF signalling and stress. The activity and subcellular localization of both DAF-16 and SKN-1 is further modulated by specific posttranslational modifications, such as phosphorylation and ubiquitination. Here, we show that ageing elicits a marked increase of SUMO levels in C. elegans. In turn, SUMO fine-tunes DAF-16 and SKN-1 activity in specific C. elegans somatic tissues, to enhance stress resistance. SUMOylation of DAF-16 modulates mitochondrial homeostasis by interfering with mitochondrial dynamics and mitophagy. Our findings reveal that SUMO is an important determinant of lifespan, and provide novel insight, relevant to the complexity of the signalling mechanisms that influence gene expression to govern organismal survival in metazoans.

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DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling

Cells ◽

10.3390/cells9010109 ◽

2020 ◽

Vol 9 (1) ◽

pp. 109 ◽

Cited By ~ 12

Author(s):

Aleksandra Zečić ◽

Bart P. Braeckman

Keyword(s):

Transcription Factors ◽

Caenorhabditis Elegans ◽

Antioxidant Defense ◽

Lifespan Extension ◽

Metabolic Shift ◽

Glyoxylate Shunt ◽

C Elegans ◽

Forkhead Box ◽

Metabolic Remodeling ◽

Transcriptional Changes

DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in Caenorhabditis elegans, integrates signals from upstream pathways to elicit transcriptional changes in many genes involved in aging, development, stress, metabolism, and immunity. The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In C. elegans daf-2 mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood. This program includes elevated antioxidant defense and a metabolic shift toward accumulation of carbohydrates (i.e., trehalose and glycogen) and triglycerides, and activation of the glyoxylate shunt, which could allow fat-to-carbohydrate conversion. The longevity of daf-2 mutants seems to be partially supported by endogenous trehalose, a nonreducing disaccharide that mammals cannot synthesize, which points toward considerable differences in downstream mechanisms by which IIS regulates aging in distinct groups.

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Flavonoids’ Effects on Caenorhabditis elegans’ Longevity, Fat Accumulation, Stress Resistance and Gene Modulation Involve mTOR, SKN-1 and DAF-16

Antioxidants ◽

10.3390/antiox10030438 ◽

2021 ◽

Vol 10 (3) ◽

pp. 438

Author(s):

María Alejandra Guerrero-Rubio ◽

Samanta Hernández-García ◽

Francisco García-Carmona ◽

Fernando Gandía-Herrero

Keyword(s):

Caenorhabditis Elegans ◽

Stress Resistance ◽

Inflammatory Diseases ◽

Biological Effects ◽

Molecular Targets ◽

Mechanistic Studies ◽

C Elegans ◽

Nutraceutical Compounds ◽

Age Related ◽

Health Promoting

Flavonoids are potential nutraceutical compounds present in diary food. They are considered health-promoting compounds and promising drugs for different diseases, such as neurological and inflammatory diseases, diabetes and cancer. Therefore, toxicological and mechanistic studies should be done to assert the biological effects and identify the molecular targets of these compounds. In this work we describe the effects of six structurally-related flavonoids—baicalein, chrysin, scutellarein, 6-hydroxyflavone, 6,7-dihydroxyflavone and 7,8-dihydroxyflavone—on Caenorhabditis elegans’ lifespan and stress resistance. The results showed that chrysin, 6-hydroxyflavone and baicalein prolonged C. elegans’ lifespan by up to 8.5%, 11.8% and 18.6%, respectively. The lifespan extensions caused by these flavonoids are dependent on different signaling pathways. The results suggested that chrysin’s effects are dependent on the insulin signaling pathway via DAF-16/FOXO. Baicalein and 6-hydroxyflavone’s effects are dependent on the SKN-1/Nfr2 pathway. In addition, microarray analysis showed that baicalein downregulates important age-related genes, such as mTOR and PARP.

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