Food & Function
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2021
·Vol. 12
·期 10
·4471-4483
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IF 5.396
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.
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Antioxidants
·
2026
·Vol. 15
·期 9
·1217
·
IF 8.2
Yuhong Huang,Meijing Wang,Yiming Zhou,Jiali Liu,Lili Ni,Ya Tan,Mengting Zhang,Jiangpeng Huang,Guolin Li,Fang Wei
Aging is a major risk factor for chronic diseases, driving an urgent need for effective geroprotectors. Repurposing psychotropic agents offers an efficient strategy to accelerate anti-aging therapeutics development. In this study, we investigated the effects of pimozide (a diphenylbutylpiperidine-class antipsychotic) on aging inCaenorhabditis elegansand elucidated the underlying mechanisms. The results demonstrated that 0.1 μM pimozide significantly extends nematode lifespan, increasing mean, median, and maximum lifespans by 44.3%, 50.0%, and 39.8%, respectively. Furthermore, pimozide improves healthspan, as evidenced by reduced age-related lipofuscin accumulation, preserved locomotor function, and decreased paralysis incidence. Moreover, pimozide-treated nematodes showed enhanced resistance to heat, ultraviolet and oxidative stress, concomitant with reduced endogenous reactive oxygen species levels. Transcriptomic profiling and biochemical validation reveal that pimozide markedly upregulates collagen gene expression and increases hydroxyproline content, indicating enhanced collagen synthesis. Mechanistically, pimozide promotes the nuclear localization of SKN-1, and its beneficial effects on lifespan extension and collagen synthesis are SKN-1-dependent, as these effects are abolished inskn-1mutants. Collectively, our findings demonstrate that pimozide promotes longevity and healthspan by activatingskn-1, which is accompanied by enhanced collagen synthesis, providing a preclinical proof of concept for its potential repurposing as a geroprotector.
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Redox Biology
·
2024
·
IF 10.7
Mengfei Chen,Zhenjun Zhu,Shujian Wu,Aohuan Huang,Zhiqing Xie,Jie Cai,Rong Huang,Shubo Yu,Ming Liu,Jumei Zhang,Yuchung Tse,Qingping Wu,Juan Wang,Yu Ding
Oxidative stress (OS) and disruption of proteostasis caused by aggregated proteins are the primary causes of cell death in various diseases. Selenopeptides have shown the potential to control OS and alleviate inflammatory damage, suggesting promising therapeutic applications. However, their potential function in inhibiting proteotoxicity is not yet fully understood. To address this gap in knowledge, this study aimed to investigate the effects and underlying mechanisms of the selenopeptide VPRKL(Se)M on amyloid β protein (Aβ) toxicity in transgenic Caenorhabditis elegans . The results revealed that supplementation with VPRKL(Se)M can alleviate Aβ-induced toxic effects in the transgenic C. elegans model. Moreover, the addition of VPRKL(Se)M inhibited the Aβ aggregates formation, reduced the reactive oxygen species (ROS) levels, and ameliorated the overall proteostasis. Importantly, we found that the inhibitory effects of VPRKL(Se)M on Aβ toxicity and activation of the unfolded protein are dependent on skinhead-1 (SKN-1). These findings suggested that VPRKL(Se)M is a potential bioactive agent for modulating SKN-1, which subsequently improves proteostasis and reduces OS. Collectively, the findings from the current study suggests VPRKL(Se)M may play a critical role in preventing protein disorder and related diseases.
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Frontiers in Microbiology
·
2024
·
IF 4
Yinyin Gao,Cheng Li,Junfei Li,Mengyao Duan,Xuan Li,Lina Zhao,Ying Wu,Shaobin Gu
Introduction: Hyperuricemia (HUA) refers to the presence of excess uric acid (UA) in the blood, which increases the risk of chronic kidney disease and gout. Probiotics have the potential to alleviate HUA.Methods: This study established a hyperuricemia model using Caenorhabditis elegans (C. elegans), and studied the anti-hyperuricemia activity and potential mechanisms of Weizmannella coagulans BC99 (W. coagulans) at different concentrations (107 CFU/mL BC99, 108 CFU/mL BC99). Subsequently, we utilized UPLC-Q-TOF/MS to investigate the impact of BC99 on endogenous metabolites in C. elegans and identified pathways and biomarkers through differential metabolomics analysis.Results: The results of this study showed that BC99 treatment significantly reduced the expression of P151.2 and T22F3.3 (p < 0.05), reduced the levels of UA and xanthine oxidase (XOD) in nematodes (p < 0.05), while extending their lifespan and movement ability (p < 0.05). Mechanistically, BC99 activates the transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing the activity of antioxidant enzymes and tolerance to heat stress in the body, and reducing the production of ROS (p < 0.001). This effect was most significant in the H-BC99 group. Furthermore, non-targeted metabolomics indicated that BC99 predominantly regulated pathways associated with amino acid metabolism (Carnosine), glycerophospholipid metabolism, and purine metabolism.Discussion: These results underscore BC99 as an effective and economical adjunct therapeutic agent for hyperuricemia, providing a scientific basis for further development and application.
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Frontiers in Pharmacology
·
2022
·
IF 5.988
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.
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Cell Communication and Signaling
·
2026
·
IF 11.6
Liu Fang,Han Chao,Xiao Yi
Histone lactylation is a recently identified epigenetic modification that directly couples cellular metabolic state with gene expression. Whether lactate affects host resistance to pathogens via histone lactylation remains unclear. Here, we found that infection with Pseudomonas aeruginosa PA14 significantly increased lactate levels in Caenorhabditis elegans . Exogenous sodium lactate (NAL) also raised lactate levels and reduced worm resistance to the extracellular bacteria P. aeruginosa and Enterococcus faecalis , but had no detectable effect on the intracellular bacteria Salmonella and Listeria monocytogenes . Lowering lactate levels with the lactate dehydrogenase inhibitor Oxamate enhanced worm resistance to infection. Genetic screening showed that the regulatory effects of NAL and Oxamate on immunity were dependent on SKN-1. Similar results were also observed with pyruvate and the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA) treatment. Mechanistic studies showed that, among the histone lactylation sites examined, elevated lactate promoted lactylation most strongly at H4K16 (H4K16la). ChIP‑qPCR results showed increased H4K16la enrichment at the skn-1 promoter upon lactate elevation. This led to increased activity of the transcription factor SKN-1, as evidenced by increased SKN-1 nuclear translocation, upregulation of downstream genes ( skn-1 , gst-4 , gst-7 , gst-10 , gcs-1 ), and enhanced GST-4::GFP fluorescence. However, the addition of NAL caused excessive GST-4::GFP fluorescence, indicating SKN-1 overactivation. This also led to suppression of the antimicrobial peptide IRG-1 and increased bacterial accumulation in the gut. In summary, this study provides evidence that lactate suppresses innate immunity in C. elegans , likely through H4K16 lactylation-mediated overactivation of SKN-1. These findings suggest that lactate may act as a negative regulator of innate immunity in an invertebrate model and provide a basis for future studies on targeting lactate metabolism or histone lactylation in infectious diseases.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 6.8
Fu-Yi Shi,Chun Li,Xi-Yang Zhang,Li-Lan Ou,Gui-Sheng Wu,Huai-Rong Luo
Ethnopharmacological relevance Corylin is a natural flavonoid isolated from the seeds of Psoralea corylifolia L., a traditional medicinal herb historically used to treat bone-related disorders such as osteoporosis. However, its role in organismal aging and the underlying molecular mechanisms remain largely unexplored. Aim of the study This study aimed to evaluate the anti-aging efficacy of corylin and elucidate the molecular basis of its action. Materials and methods Using Caenorhabditis elegans ( C. elegans ) as a model organism, we systematically assessed the impact of corylin on lifespan and multiple aging-associated phenotypes, including locomotor capacity, muscle integrity, lipofuscin accumulation, and resistance to thermal, pathogenic, and oxidative stress. Neuroprotective potential was evaluated using transgenic models of Parkinson's and Huntington's diseases. To uncover the mechanisms involved, we analyzed the DAF-16/SKN-1 signaling axis and autophagy-related processes using transgenic reporter strains, RNA interference, and RT-qPCR. Results Corylin treatment significantly extended lifespan, improved locomotor performance, and reduced lipofuscin accumulation. Furthermore, it enhanced resistance to environmental stresses and conferred neuroprotection in models of neurodegeneration. Mechanistically, corylin promoted nuclear translocation of DAF-16 and upregulated the expression of DAF-16/SKN-1 target genes. This transcriptional activation was associated with enhanced autophagic flux and improved mitochondrial quality. Crucially, the beneficial effects of corylin were abolished in daf-16 and skn-1 mutants, as well as under autophagy-deficient conditions. Conclusion Corylin exerts multifaceted anti-aging effects in C. elegans by coordinately activating the DAF-16/SKN-1 signaling axis, thereby enhancing autophagic flux and maintaining mitochondrial homeostasis. These findings identify corylin as a promising natural candidate for aging intervention.
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Antioxidants
·
2021
·Vol. 10
·期 11
·1697
·
IF 6.313
Shiling Feng,Chunyan Zhang,Tao Chen,Lijun Zhou,Yan Huang,Ming Yuan,Tian Li,Chunbang Ding
Oleuropein (OLE) is a secoiridoid glycoside that mainly exists in olives with multifaceted health benefits. The present study aimed to investigate the stress resistance and lifespan extension effects of OLE inCaenorhabditis elegans. The results showed that OLE could significantly prolong the lifespan ofC. elegansby 22.29%. Treatment with OLE also significantly increased the survival rates of worms against lethal heat shock and oxidative stress. Meanwhile, OLE supplementation increased the expression and activity of antioxidant enzymes and suppressed the generation of malondialdehyde in nematodes. In addition, the results from mutants implied that OLE might mediate longevity and stress resistance via DAF-16/FoxO, which played a vital role in the insulin/IGF-1 signaling (IIS) pathway. To further identify the molecular targets of OLE, mRNA level and loss-of-function mutants of IIS-associated genes were investigated. The data revealed that OLE activated IIS by down-regulating the upstream components,daf-2andage-1. Furthermore, another stress response and longevity pathway in parallel to DAF-16, SKN-1/Nrf2, was also shown to involve in OLE-induced beneficial effects. Collectively, these results provide the theoretical basis that OLE could enhance the stress resistance and increase the lifespan ofC. elegansthrough the IIS and SKN-1/Nrf2 signaling pathways.Keywords:oleuropein;Caenorhabditis elegans;longevity;stress resistance
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JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
·
2024
·
IF 3.7
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.
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AGING CELL
·
2023
·
IF 7.8
Chaweewan Sirakawin,Dongfa Lin,Ziyue Zhou,Xiaoxin Wang,Rhianne Kelleher,Shangyuan Huang,Weimiao Long,Andre Pires-daSilva,Yu Liu,Jingjing Wang,Ilya A. Vinnikov
Vitamin A (VA) is a micronutrient essential for the physiology of many organisms, but its role in longevity and age-related diseases remains unclear. In this work, we used Caenorhabditis elegans to study the impact of various bioactive compounds on lifespan. We demonstrate that VA extends lifespan and reduces lipofuscin and fat accumulation while increasing resistance to heat and oxidative stress. This resistance can be attributed to high levels of detoxifying enzymes called glutathione S-transferases, induced by the transcription factor skinhead-1 (SKN-1). Notably, VA upregulated the transcript levels of skn-1 or its mammalian ortholog NRF2 in both C. elegans , human cells, and liver tissues of mice. Moreover, the loss-of-function genetic models demonstrated a critical involvement of the SKN-1 pathway in longevity extension by VA. Our study thus provides novel insights into the molecular mechanism of anti-aging and anti-oxidative effects of VA, suggesting that this micronutrient could be used for the prevention and/or treatment of age-related disorders.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Weimin Zuo,Tingting Lin,Hehuan Zhu,Xiaobi Huang,Yudong Guo,Qihe Long,Yanfeng Liang,Yongyang Chen,Xiaoqing Xu,Yanhong Su,Wenmei Su
As a widely used chemical raw material, the potential exposure threat of bisphenol A is inevitable. At present, there is no effective treatment for the toxicity caused by bisphenol A (BPA). Therefore, it is necessary to find a natural drug to alleviate the toxicity of BPA. In this study, Caenorhabditis elegans was applied to evaluate the protective effect of tremella polysaccharide (TPC) on BPA. The results showed that TPC regained the locomotion and chemotaxis ability induced by BPA. Also TPC protected the dopamine neuron cells against the BPA-induced damage. Moreover, TPC also regulated IIS/PI3K/AKT and MAPK/AMPK pathways to activate daf-16 and skn-1 (homolog to Nrf-2) increase the antioxidant ability in C. elegans . TPC treatment obviously increased the expression of GST-4 as well as the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) to sharply reduced the high reactive oxygen species (ROS) level to help the C. elegans to against the toxicity induced by BPA. Altogether, these results indicated TPC is a promising natural drug to alleviate the toxicity induced by BPA.
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BIOGERONTOLOGY
·
2026
·Vol. 27
·期 2
·72
·
IF 5.3
Zhang Xiaoli,Wang Chengniu,Chen Weiguan
Aging is a major risk factor for the onset and progression of many neurodegenerative diseases. Inflammation is the body’s natural defense mechanism against harmful stimuli . A growing body of research has highlighted the intricate relationship between aging and inflammation, with chronic low - grade inflammation, often referred to as “inflammaging,” being a hallmark of the aging process. Cycloneolitsol (CL) is a C-32 cycloartane-type triterpene from Taxodium ascendens which has been reported to possess the anticancer, neuroprotection and antibacterial activities. Its specific role and the underlying molecular mechanisms in modulating the aging process remain unclear. Our study aimed to explore the possible anti-aging effect and mechanisms of CL. Network pharmacology predicted core targets and several potential pathways, which are associated with the anti-aging effect of CL. RAW264.7 macrophages and Caenorhabditis elegans were selected for evaluating its anti-aging and anti-inflammation activity. The results showed that CL exerted obvious anti-inflammatory effects against LPS-induced M1-type polarization of RAW264.7 cells via NF-κB signaling pathway. In C. elegans , CL improved Biological Characteristics and prolonged the lifespan without reproductive toxicity. Furthermore, experiments on different mutant C. elegans strains and the nuclear translocation of SKN-1 confirmed that CL activates autophagy and enhances the antioxidant stress response ability through the SEK-1/PMK-1/SKN-1 signaling pathway. This study provides novel insights into the biological activities of CL, highlighting its potential as a natural product for treating inflammation-related diseases and delay aging.
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