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Frontiers in Pharmacology · 2022 · IF 5.988

Alpiniae oxyphylla fructus extract promotes longevity and stress resistance of C. elegans via DAF-16 and SKN-1

Xiao Man,Chen Bocen,Niu Kun,Long Ziyu,Yang Fan,Xie Yiqiang

Background: Alpiniae Oxyphylla Fructus (AOF) is Traditional Chinese medicine and a dietary supplements for centuries, which posseses cardiotonic, neuroprotective, antioxidant, warming the kidney and nourish the spleen, these biological fuction is related to potential anti-aging properties. However, little is known about their effects on aging. This work aimed to investigate the effects of extracts of AOF on longevity and stress resistance in Caenorhabditis elegans (C. elegans) and the mechanisms that underlie its effects.Methods: Wild-type (WT) strand of C.elegans (N2)worms were cultured in growth medium with or without AOF. First, we examined the effects of AOF on lifespan, reproduction and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, The levels of ROS and MDA, the antioxidant enzyme activities were examined to explore the underlying mechanism of AOF. Finally, the expression of the longevity-related genes were investigated to further understand the AOF’s underlying mechanism.Results: The lifespan of C. elegans was prolonged by 23.44% after treatment with high-dose AOF (100 ug/ml). AOF alleviated aging-related declines in C. elegans health and enhanced resistance to heat shock. Furthermore, AOF decreased reactive oxygen species and malondialdehyde, increased the activities of superoxide dismutase and catalase, and reduced accumulation of fat. AOF upregulated the expression of sod-3, gst-4, daf-16, and skn-1 but downregulated the expression of daf-2 and age-1 and accelerated the translocation of DAF-16 into the nucleus. The extended lifespan induced by AOF was reversed in daf-16(mu86) and skn-1(zu135) mutants, indicating that this gene is involved in AOF-regulated longevity.Conclusion: Our findings demonstrated that AOF extends lifespan and healthspan and enhances stress via boosting the activity of the antioxidant enzyme and controlling the expression of genes associated with insulin/IGF signaling and SKN-1 pathways. As a result, this work suggested AOF as a possible candidate to reduce the signs of aging by activating and inhibiting target genes.

CAS / MDL: 1910-42-5
研究领域: 老年学 · 分子生物学 · 中医药学 · 遗传学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMEDICINE & PHARMACOTHERAPY · 2022 · IF 7.419

H-2 increases oxidative stress resistance through DAF-16/FOXO pathways in Caenorhabditis elegans: A new approach to vitiligo treatment

Xingzhuo Song,Yu Du,Cen Liu,Wei Wang,Jing Han,Xinlou Chai,Yonggang Liu

Oxidative stress disrupts the homeostasis of the redox state in cells and induces apoptosis. Prolonged oxidative stress can impair the normal function of cells, tissues, and organs and lead to the development of several diseases. H-2 was synthesized by derivatising N- Alkylamides (NAAs) from Anacyclus pyrethrum (L.) DC, which is commonly used in the treatment of vitiligo in Uyghurs. The antioxidant activity and potential molecular mechanisms of H-2 were investigated using Caenorhabditis elegans ( C. elegans ) and mouse melanoma cell B16-F10 models. The in vivo anti-vitiligo activity of H-2 was studied using C57BL/6 mice. The results showed that H-2 could increase the survival time of nematodes under oxidative stress, promote the nuclear localization of DAF-16, and enhance the expression of Superoxide Dismutase 3 (SOD-3) in nematodes thereby activating the antioxidant enzyme system. H-2 could affect the survival rate of age-1 and akt-1 mutants under oxidative stress. H-2 could reverse the oxidative stress damage by reducing the reactive oxygen species (ROS) content in the Hydrogen peroxide (H 2 O 2 ) -induced oxidative stress damage model of mouse melanoma cells B16-F10. In addition, it was also able to increase the number of melanocytes in the hair follicles of vitiligo model mice and improve the phenomenon of skin damage in mice. In conclusion, our findings suggest that H-2 can alleviate oxidative stress damage in C. elegans and B16-F10, which may be associated with oxidative stress, suppression of antioxidant defences, and transcription factors DAF-16/FOXO, providing beneficial evidence for the application of H-2 in the vitiligo treatment.

研究领域: 分子生物学 · 药理学 · 皮肤病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Lycium ruthenicum Murray exosome-like nanovesicles alleviated Alzheimer's disease–like symptoms induced by Aβ protein in transgenic Caenorhabditis elegans through the DAF-16 pathway

Yadan Zhang,Xiaoyu Zhang,Jie Zhou,Yuting Li,Tianhan Kai,Lin Zhang

Alzheimer's disease (AD) is predominantly characterized by cholinergic dysfunction, mitochondrial impairment, oxidative stress, and inflammation, primarily driven by amyloid-beta (Aβ) peptides. This study investigates the protective effects of Lycium ruthenicum Murray–derived exosome-like nanoparticles (LELN) in AD models using transgenic Caenorhabditis elegans ( C. elegans ). Findings showed that C. elegans effectively internalized LELN, which remained stable in vivo. Compared with untreated controls, treatment with 600 μg/mL LELN significantly extended the lifespan of CL4176 [ myo-3p ::Aβ 1–42 ] and CL2006 [ unc-54 /Aβ 1–42 ] worms by 34.78 % and 34.85 %, respectively, and delayed Aβ-induced paralysis by 52.42 % and 42.72 %, respectively. Furthermore, LELN increased the chemotaxis index of CL2355 [ snb-1 ::Aβ 1–42 ] worms from 11.11 % to 55.56 %. Mechanistically, LELN reduced the levels of Aβ oligomers and monomers via the DAF-16 pathway, consequently alleviating AD-like symptoms in transgenic C. elegans . The effects of LELN include inhibiting acetylcholinesterase activity to mitigate cholinergic dysfunction, restoring mitochondrial membrane potential and adenosine triphosphate production to ameliorate mitochondrial dysfunction, and reducing oxidative stress and inflammation. Collectively, these results highlight the protective role of LELN against Aβ-induced AD pathology and underscore their potential as a therapeutic candidate for AD treatment.

CAS / MDL: 14769-73-4
研究领域: 神经生物学 · 分子生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHOTOCHEMISTRY AND PHOTOBIOLOGY · 2024 · IF 2.6

Astaxanthin attenuates UV-irradiation aging process via activating JNK-1/DAF-16 in Caenorhabditis elegans

Xiuping Lin,Chang-sheng Shao,Shereen M. Elsherbiny,Qing Huang

Astaxanthin (AST) is a xanthophyll carotenoid with strong oxidation resistance, which can effectively scavenge various free radicals and protect organisms from oxidative damage. AST is also known to have prominent anti-aging effects, but the underlying mechanism of AST in anti-radiation aging is largely unknown. In this work, we applied ultraviolet (UV) irradiation to accelerate the aging of Caenorhabditis elegans ( C. elegans ) and treated the nematodes with AST to explore whether and how AST could attenuate the radiation-induced aging effect. Our results showed that AST improved the survival rate of C. elegans , reduced the aging biomarkers, and alleviated the mitochondrial dysfunction caused by the irradiation. Based on the transcriptome sequencing analysis, we identified that the key genes regulated by AST were involved in JNK-MAPK and DAF-16 longevity signaling pathways. Furthermore, we employed jnk-1 and daf-16 mutants and verified the role of the JNK-1/DAF-16 signaling pathway in the anti-aging effect. As such, this study has not only demonstrated that AST can resist the aging process caused by UV-irradiation but also revealed the anti-aging mechanism of AST through JNK-1/DAF-16 activation in C. elegans.

CAS / MDL: 472-61-7
研究领域: 分子生物学 · 衰老研究 · 遗传学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MECHANISMS OF AGEING AND DEVELOPMENT · 2022 · IF 5.498

Cyanidin-3-O-glucoside promotes stress tolerance and lifespan extension of Caenorhabditis elegans exposed to polystyrene via DAF-16 pathway

Wen Chen,Zhen Chen,Shuo Shan,Aibo Wu,Chao Zhao,Xiang Ye,Xiaodong Zheng,Ruiyu Zhu

Microplastic pollution has attracted growing attention due to its prevalent and persistent exposure to general population through the food chain, but few reports have focused on the toxicological prevention of polystyrene (PS). Using the wild-type and mutant strains, this study explored the impacts of PS and cyanidin-3-O-glucoside (C3G) on stress tolerance and lifespan of Caenorhabditis elegans ( C. elegans ). In N2 nematodes, PS exposure initiated the oxidative stress and subsequent lifespan reduction, while these adverse impacts could be positively improved by C3G treatment. Considering the pivotal role of DAF-16 pathway in stress tolerance and lifespan regulation, the expression of the daf-16 gene and its downstream antioxidant genes ( clt-2 , hsp-16.1 , sod-3 , sod-5 ) were examined, and found to be significantly enhanced by C3G. Since the sod-3 gene was up-regulated the most fold by C3G, the activity of SOD enzyme that encoded by the sod-3 was examined, and could be obviously enhanced upon C3G treatment. This explained the improved oxidative stress and delayed oxidation-associated aging after C3G intervention. Nevertheless, these positive effects of C3G were weakened in daf-16 (-) mutant strain (with deleted DAF-16 gene), for which the beneficial effects of C3G in promoting stress resistance and lifespan extension were inhibited. These findings suggested that the DAF-16 gene and its downstream antioxidant genes, have participated in C3G’s regulations on redox balance and lifespan that impacted by nano-polystyrene particles. This study highlighted the link between dietary components and environmentally driven disturbance.

研究领域: 环境科学 · 分子生物学 · 毒理学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

Barley β-glucan resist oxidative stress of Caenorhabditis elegans via daf-2/daf-16 pathway

Xiang Xiao,Yurong Zhou,Cui Tan,Juan Bai,Ying Zhu,Jiayan Zhang,Xinghua Zhou,Yansheng Zhao

β-glucan is an important functional active component with relatively high content in barley. It is reported to possess various biological activities, including anti-oxidative stress, but its mechanism of action remains obscure. In the current study, C. elegans was used as an in vivo animal model to explore its anti-oxidative stress mechanism. We found that both RBG (raw barley β-glucan) and FBG (fermented barley β-glucan) could significantly reduce the ROS level in C. elegans under oxidative emergency conditions. In addition, both FBG and RBG had positive effects on SOD and CAT enzyme activity, and FBG treatment obviously reduced the MDA content in nematodes under oxidative stress. Moreover, FBG and RBG pretreatment could extend the median lifespan of C. elegans under oxidative stress. The CB1370 and CF1038 mutants further confirmed that daf-2 and daf-16 were necessary for FBG or RBG to participate in anti-oxidative stress, and the RT-PCR results also evidenced that β-glucans resist oxidative stress in C. elegans partially through the daf-2 / daf-16 pathway. In summary, barley β-glucan has high potential to defense oxidative stress as a natural polysaccharide.

CAS / MDL: 1910-42-5
研究领域: 分子生物学 · 遗传学 · 营养科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2021 ·Vol. 12 ·期 10 ·4471-4483 · IF 5.396

Rhodiola extract promotes longevity and stress resistance of Caenorhabditis elegans via DAF-16 and SKN-1

Siqi Jiang,Na Deng,Bisheng Zheng,Tong Li,Rui Hai Liu

The effects of Rhodiola extract (RE) on longevity and stress resistance in Caenorhabditis elegans (C. elegans), and the underlying molecular mechanisms were explored in the present study. Results showed that the lifespan of C. elegans was remarkably prolonged by 37.1% after treated with high-dose RE (480 μg mL−1). Intervention with RE alleviated aging-related declines in the C. elegans model, and enhanced the stress resistance against heat shock, ultraviolet radiation and paraquat. Moreover, RE reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and catalase (CAT). RE also upregulated the gene expression of sod-3, gst-4, daf-16, skn-1 in C. elegans, downregulated the gene expression of daf-2 and age-1, and accelerated the translocation of DAF-16 and SKN-1 into the nucleus. Furthermore, the daf-16(mu86) and skn-1(zu169) mutants reversed the extension of lifespan triggered by RE, indicating that these genes were involved in RE-regulated longevity. These results demonstrated that RE could enhance lifespan extension, healthspan and stress resistance of C. elegans via insulin/IGF signaling and SKN-1 pathways. Therefore, the present findings suggested Rhodiola as a potential candidate to ameliorate the symptoms of aging.

CAS / MDL: 1910-42-5
研究领域: 老年学 · 分子生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2025 · IF 8.3

Hickory nut polyphenols enhance oxidative stress resilience and improve the longevity of Caenorhabditis elegans through modulating DAF-16/DAF-2 insulin/IGF-1 signaling

Song Wang,Chenyu Jiang,Shitong Yu,Qianru Fan,Kai Yang,Jianqin Huang,Yan Li

Background Hickory ( Carya cathayensis ) nuts, renowned for their health benefits and delightful taste, contain abundant bioactive compounds, particularly polyphenols. However, the specific mechanisms underlying their antioxidant properties and anti-aging effects remain elusive. Purpose This study aims to investigate the effects of hickory nut polyphenols (HNP) on oxidative stress mitigation and aging modulation. Methods The innovative integration of medium-pressure liquid chromatography (MPLC) with in vitro bioactive screening was employed to discover an optimized HNP fraction (HNP3–2). Anti-aging effects of HNP3–2 on Caenorhabditis elegans ( C. elegans ) were determined through lifespan analysis, lipofuscin accumulation quantification, and motility assessments. Oxidative stress resistance was further evaluated by detecting the reactive oxygen species (ROS) contents, lipid peroxidation, and antioxidase activities. Integrative approaches combining transcriptomic, qRT-PCR, GFP reporter strains, and gene knockout mutants were utilized to explore the potential regulatory mechanisms. Non-targeted metabolomics was employed to conduct a comprehensive profiling analysis of HNP and their bioactive fractions. Results HNP3–2 significantly decreased ROS production, lipofuscin accumulation, and lipid peroxidation, while enhanced the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). It also conferred robust protection against oxidative stress induced by H 2 O 2 and juglone. HNP3–2 regulated lifespan extension mainly via the DAF-16/-2 insulin/IGF-1 signaling (IIS), which was further validated using loss- and gain-of-function mutants including age-1, akt-1/2, daf-2 , and daf-16 , as well as worms overexpressing SOD-3, GST-4, and DAF-16. Metabolomic analysis identified 31 kinds of polyphenol compounds displaying abundance patterns congruent with the overall antioxidant potency in vitro. Conclusion This study first reveals the efficacy of HNP as a promising antioxidant and anti-aging intervention. Notably, the screened bioactive fraction HNP3–2 acts primarily by modulating the DAF-16/DAF-2 insulin/IGF-1 signaling cascade, operating through a mechanism independent of dietary restriction. Collectively, these findings position HNP as a breakthrough candidate for next-generation gerotherapeutics, with translational potential for advancing human aging research.

研究领域: 生物化学 · 分子生物学 · 衰老研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOGERONTOLOGY · 2025 ·Vol. 27 ·期 1 ·6 · IF 4.1

Multi-target synergistic anti-aging: QG extends Caenorhabditis elegans lifespan through DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming

Wang Jiahui,Li Shuqi,Lei Zichen,Xing Yantao,Li Jieshu,Guo Jie,Duan Boshi,Liu Yonggang

Aging not only significantly reduces the quality of life for the elderly but also poses multifaceted challenges to society. Its progression involves the synergistic interaction of multidimensional, multipathway molecular mechanisms, including mitochondrial dysfunction, oxidative stress accumulation, chronic inflammation, and genomic damage. Quercetagetin (QG), as a natural flavanol monomer, exhibits significant potential in anti-aging due to its simultaneous targeting of key aging pathways such as oxidative stress and chronic inflammation. We first evaluated QG’s safety profile, finding that 0.02 mg/ml QG did not adversely affect motility, feeding, growth, and reproductive capacity in Caenorhabditis elegans ( C. elegans ). At this concentration, in vivo experiments using wild-type C. elegans confirmed QG’s ability to extend lifespan and enhance oxidative stress resistance. The antioxidant and anti-aging effects of QG were further validated using the daf -16 mutant C. elegans DR26. Subsequently, observation of QG’s impact on C. elegans mitochondrial morphology revealed significant reductions in area/perimeter and mitochondria coverage ratio following treatment. This indicates that QG treatment shifts the mitochondrial network from fusion toward fission and reduces overall mitochondrial content. QG can also improve age-related dopaminergic, 5-hydroxytryptaminergic and cholinergic neuron degeneration. Mass spectrometry metabolome analysis revealed that QG significantly affected citrate cycle and glycerophospholipid metabolism. Collectively, QG extends C. elegans lifespan by regulating redox homeostasis, DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming. This multi-target regulatory capacity positions QG as an ideal candidate molecule for anti-aging drug development.

CAS / MDL: 51-21-8
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Nutrition · 2022 · IF 6.59

Sea cucumber (Acaudina leucoprocta) peptides extended the lifespan and enhanced antioxidant capacity via DAF-16/DAF-2/SOD-3/OLD-1/PEPT-1 in Caenorhabditis elegans

Wu Yue,Yang Jingjuan,Xu Chengmei,Li Qiuqi,Ma Yage,Zhao Shenglan,Zhuang Jiachen,Shen Fei,Wang Qianqian,Feng Fengqin,Zhang Xi

The sea cucumber peptides (SCPs) from Acaudina leucoprocta were derived from the patented bio-enzyme digestion technology and the molecular weight of obtained SCPs was <10 kDa. In this study, we investigated the possible anti-aging effects of SCPs on the model of Caenorhabditis elegans and the underlying mechanisms. SCPs extend the average lifespan of nematodes by 31.46%. SCPs enhance the anti-stress capacity of C. elegans by improving heat resistance and mobility, Also, the accumulated potential oxidative stress inducers like lipofuscin and reactive oxygen species (ROS) were reduced to 40.84 and 71.43%. In addition, SCPs can increase the antioxidant capacity in nematodes by enhancing the activity of SOD and CAT and reducing MDA accumulation in nematodes to 32.44%. Mechanistically, SCPs could mediate DAF-16/DAF-2/SOD-3/OLD-1/PEPT-1 axis to improve antioxidant capacity and extend lifespan in nematodes. Taken together, these findings provide a direction for the anti-aging effects of sea cucumber peptides and new insights into the further purifications of SCPs and future research on aging.

研究领域: 老年学 · 分子生物学 · 营养保健品
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY · 2024 · IF 3.7

Ovalbumin promotes innate immune response of Caenorhabditis elegans through DAF-16 and SKN-1 pathways in insulin/IGF-1 signaling

Pei Haibing,Lin Zhiyin,Yao Kexin,Luo Yeqing,Tong Ping,Chen Hongbing,Wu Yong,Wu Zhihua,Gao Jinyan

Ovalbumin (OVA) is a major allergen in eggs and could induce severe allergic reactions in sensitive individuals, where the innate immune system works as a regulator. The mechanism of how innate immunity adjusts to food allergy is relatively well-studied, however, the effects of allergen uptake on the innate immune system remain unclear. Therefore, the Caenorhabditis elegans ( C. elegans ) model was utilized to assess the effects of OVA on its innate immune system. OVA enhanced the immune response of C. elegans with higher survival rates under Pseudomonas aeruginosa infection. Moreover, sustaining OVA treatment improved the health states that were reflected in the prolonged lifespan, alleviated oxidative stress, accelerated growth, and promoted motility. RNA-sequencing analysis and the slow-killing assays in the mutants of insulin/IGF-1 signaling (IIS)-related genes confirmed that IIS was necessary for OVA to regulate innate immunity. Besides, OVA activated SKN-1 temporarily and facilitated the nuclear localization of DAF-16 for improving immunity and health status in C. elegans . Together, OVA could enhance the innate immune responses via DAF-16 and SKN-1 pathways in the IIS of C. elegans , and this work will provide novel insights into the regulation of innate immunity by OVA in higher organisms.

CAS / MDL: 3326-32-7
研究领域: 免疫学 · 分子生物学 · 遗传学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2021 · IF 10.588

Tris(1,3-dichloro-2-propyl) phosphate reduces longevity through a specific microRNA-mediated DAF-16/FoxO in an unconventional insulin/insulin-like growth factor‑1 signaling pathway

Chen Wang,Yeyong Li,Lingjun Zeng,Chongli Shi,Yi Peng,Hui Li,Haibo Chen,Jun Yu,Jin Zhang,Biao Cheng,Ruolin Pan,Xiaoli Wang,Minghui Xiang,Yuan Huang,Yongdi Liu

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has received concerns due to its frequent detection in environmental media and biological samples. Our previous study has indicated TDCPP reduced the lifespan of Caenorhabditis elegans ( C. elegans ) by triggering an unconventional insulin/insulin-like growth factor signaling (IIS) pathway. This study continued to investigate the possible deleterious effects of TDCPP relating to longevity regulation signal pathways and biological processes. Specifically, this study uniquely performed small RNA transcriptome sequencing (RNA-seq), focusing on the underlying mechanisms of TDCPP-reduced the longevity of C. elegans in-depth in microRNAs (miRNAs) . Based on Small RNA-seq results and transcript levels of mRNA involved in the unconventional IIS pathway, a small interaction network of miRNAs-mRNAs following TDCPP exposure in C. elegans was preliminarily established. Among them, up-regulated miR-48 and miR-84 ( let-7 family members) silence the mRNA of daf-16 (the crucial member of the FoxO family and pivotal regulator in longevity) via post-transcription and translation dampening abilities, further inhibit its downstream target metallothionein-1 ( mtl-1 ), and ultimately contributed to the reduction of nematode longevity and locomotion behaviors. Meanwhile, the high binding affinities of TDCPP with miRNAs cel-miR-48–5p and cel-miR-84–5p strongly support their participation in the regulation of nematode mobility and longevity. These findings provide a comprehensive analysis of TDCPP-reduced longevity from the perspective of miRNAs.

研究领域: 毒理学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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