Search Results (116)

Buds are continuously renewed sensory organs in which development, adult maintenance, and repair share overlapping molecular circuitry. During embryogenesis, WNT/β-catenin signaling promotes taste placode formation and placodal Shh expression, while SHH refines papilla spacing and restricts neighboring papilla formation. SOX2 functions as a taste-competence and progenitor maintenance factor. In adults, LGR5/LGR6–RSPO–WNT signaling sustains progenitor activity, and gustatory neurons are an important source of RSPO2; available genetic evidence is consistent with a neuron-derived contribution to the LGR5/LGR6 niche, and AAV-Cre-mediated neuron-specific ablation of Rspo2 in the petrosal ganglion led to near-complete loss of circumvallate taste buds. HH signaling from epithelial and neuronal sources further supports SOX2-dependent progenitor homeostasis. Lineage allocation is governed by transcriptional programs that include POU2F3/SKN-1a for sweet, umami, and bitter type II taste receptor cells, and ASCL1 with posterior-field NKX2-2 for type III presynaptic/sour cells. After denervation or irradiation, regeneration depends primarily on LGR5⁺/KRT14⁺ progenitors and may be supplemented, in specific injury contexts, by plasticity of a subset of K8-lineage taste receptor cells that acquire KRT14/SOX2/PCNA progenitor-like features. Key unresolved questions include the direct chromatin targets of taste lineage regulators (which remain to be defined by ChIP-seq in native taste progenitors), the identity of the type I cell selector, the contribution of dedifferentiation across injury models, and the degree to which mouse-derived networks are conserved in human taste biology. Full article

In this study, polysaccharides from Ficus carica L. fruits (FCPs) were extracted using a deep eutectic solvent (DES)-based ultrasound-assisted extraction (UAE) method. The physicochemical properties of the FCPs were then characterized, and the anti-aging effects of FCPs were evaluated in Caenorhabditis elegans (C. elegans). It was demonstrated that FCPs significantly extended the lifespan of the nematodes, while improving locomotor activity without affecting the body size or reproductive capacity. Meanwhile, FCPs reduced lipofuscin accumulation, decreased intracellular reactive oxygen species (ROS) levels, and increased the survival of C. elegans under oxidative stress. Moreover, FCPs upregulated the expression of antioxidant genes sod-1, sod-3, ctl-2, ctl-3 and gst-4. The expression of skinhead-1 (skn-1), a homologue gene of mammalian nuclear factor erythroid 2-related factor (Nrf) in C. elegans, was also elevated upon FCPs treatment. Knockdown of skn-1 expression by RNA interference abolished the lifespan extension and ROS reduction in FCPs-treated C. elegans, indicating that the SKN-1-mediated signaling was essential for the anti-aging effects of FCPs. Additionally, FCPs caused downregulation of the key components of the insulin/IGF-1 signaling (IIS) pathway, age-1, akt-1, and akt-2. Overall, these results suggested that FCPs promoted longevity in C. elegans via modulation of SKN-1 and IIS pathway. Full article

Parkinson’s disease (PD) involves oxidative stress, proteotoxic aggregation, and neurotransmitter dysfunction, yet current therapies remain largely symptomatic. This study investigated whether Jujube polysaccharides (ZJP), a food-derived polysaccharide, confer neuroprotective and anti-aging benefits in Caenorhabditis elegans. ZJP was characterized for physicochemical features, antioxidant capacity, and in vivo safety. Effects were evaluated in wild-type N2 and PD models by measuring lifespan, locomotion, pharyngeal pumping, chemotaxis, α-syn::YFP fluorescence intensity, dopaminergic neuron integrity, adenosine triphosphate (ATP), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and lipofuscin. Stress resilience was assessed under heat (37 °C) and H₂O₂ exposure. RT-qPCR profiled genes related to stress responses and neurotransmission. ZJP showed no detectable toxicity at tested doses. ZJP extended mean lifespan in N2 (10.3–14.1%) and NL5901 (9.1%), improved locomotion, pharyngeal pumping, and chemotaxis, reduced lipofuscin (26.8–50.6%), and increased survival under heat (23.6%) and oxidative stress (38.1%). In PD models, ZJP reduced α-syn::YFP fluorescence by up to 54.9%, protected dopaminergic neurons, and increased ATP. It also lowered ROS and MDA levels while raising SOD and CAT activities. Gene expression changes were associated with enhanced oxidative stress resistance and with altered expression of genes involved in SKN-1/DAF-16-related stress-response signaling. These findings provide preliminary evidence that ZJP may promote longevity, stress resilience, and neuroprotection in C. elegans models of PD, supporting its potential as a candidate for further investigation in neuroprotection. Full article

Background: This study aimed to investigate the anti-aging mechanisms of Alpinia oxyphylla polysaccharides (AOFs) through integrated in vivo experiments, network pharmacology, and molecular docking. Methods: Three purified fractions (AOF1, AOF2, and AOF3) were structurally characterized for monosaccharide composition and molecular weight. Anti-aging and antioxidant activities were evaluated using Caenorhabditis elegans, followed by gene expression analysis, network pharmacology target identification, and molecular docking validation. Results: All AOFs significantly extended lifespan, enhanced resistance to oxidative and heat stress, reduced reactive oxygen species and lipid peroxidation, and upregulated superoxide dismutase and catalase activities. Gene expression analysis revealed activation of the insulin/insulin-like growth factor signaling pathway through upregulation of daf 16, skn 1, sod 3, ctl 1, and hsp 16.2. Network pharmacology identified 254, 85, and 119 core targets for AOF1, AOF2, and AOF3 respectively, enriched in PI3K/AKT, MAPK, hypoxia, and xenobiotic response pathways. KEGG analysis further implicated lipid and atherosclerosis, HIF 1, FoxO, and PI3K Akt signaling. Molecular docking showed that critical monosaccharides and metformin formed stable hydrogen-bonded complexes with AKT1, INS, SRC, and STAT3. Among the fractions, AOF1 and AOF3 exhibited superior activities. Conclusions: These findings demonstrate the multi-target, multi-pathway anti-aging actions of AOFs and support their potential as natural antioxidants and functional food ingredients for anti-aging therapeutics. Full article

Paederia scandens (Lour.) Merr is a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects of paederoside (PSG) have not been thoroughly investigated; therefore, in this study, Caenorhabditis elegans (C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan of C. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant gene skn-1 and longevity-associated gene daf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited in C. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component of Paederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feeding C. elegans PSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug. Full article

Despite growing concerns about the ecological and health risks of nanoplastics at environmentally relevant concentrations (ERCs), the effects of polyurethane nanoplastics (PU NPs) on environmental organisms remain unclear. This study assessed the toxicity of PU NPs in the μg/L range in Caenorhabditis elegans (C. elegans) through chronic exposure. Our results showed that 10 μg/L PU NP exposure significantly reduced brood size, head thrashes, and body bends, while 100 μg/L PU NP exposure decreased lifespan, and 1000 μg/L PU NP exposure increased mortality in wild-type C. elegans. Analysis of oxidative stress showed that both 10 and 1000 μg/L PU NP exposures elevated reactive oxygen species (ROS), SKN-1::GFP, and GST-4::GFP levels. Notably, while ROS production rose at 1000 μg/L, SKN-1::GFP and GST-4::GFP expression decreased compared to the 10 μg/L group, suggesting a compensatory response in C. elegans at lower exposure levels. The expression of oxidative stress-related genes and phenotype of differentially expressed genes indicated that C. elegans was in a compensatory phase when exposed to 10 μg/L of PU NPs, participating in the protective response of C. elegans to PU NPs. However, when exposed to 1000 μg/L of PU NPs, C. elegans was in a decompensatory phase, participating in the toxic regulation of PU NPs. In addition, under 10 μg/L PU NP exposure, cinnamon essential oil (CIEO) can enhance the expression of more antioxidant enzymes, thereby increasing the protective effect. Under 1000 μg/L PU NP exposure, CIEO could alleviate the toxic response of C. elegans to PU NPs exposure by promoting the expression of skn-1. Molecular docking analysis showed that the main active component of CIEO, cinnamaldehyde (CID), has a strong affinity with SKN-1/Nrf2. Our study is the first to emphasize the toxic effects of PU NPs on environmental organisms at ERCs and that CIEO might serve as a potential antidote for nanoplastic poisoning. Full article

3,4-Dihydroxybenzaldehyde (DBD) is a polyphenolic active constituent derived from Gastrodia elata. Its characteristic phenolic structure is associated with diverse bioactivities, such as anti-inflammatory, antioxidant, and cardioprotective effects. However, its role and underlying mechanisms in combating Alzheimer’s disease (AD) remain inadequately elucidated. In this study, we employed computational and experimental approaches to investigate the anti-AD effects of DBD. Molecular dynamics simulations revealed that DBD binds to Aβ fibrils via π–π stacking, hydrophobic interactions, and hydrogen bonds, suggesting its potential to disrupt Aβ fibril stability and thereby inhibit aggregation. In vivo experiments in an AD C. elegans model demonstrated that 2 mM DBD treatment significantly delayed paralysis and extended lifespan. It also improved locomotor activity and pharyngeal pumping rates, while reducing lipofuscin accumulation. These results collectively suggest that DBD promotes healthspan-associated phenotypes. Broad-targeted metabolomics analysis indicated that DBD significantly altered the metabolic profile of the worms. Further mechanistic investigations suggested that the protective effects of DBD are associated with the activation of the DAF-16/FOXO and SKN-1/Nrf2 signaling pathways, accompanied by enhanced resistance to oxidative and thermal stress in nematodes. These findings suggest that DBD exhibits anti-AD potential through multimodal mechanisms, which involve interference with Aβ toxicity and reinforcement of cellular defense. This study supports DBD as a candidate compound and provides a rationale for its further investigation. Full article

Obesity is among the top contributing factors for non-communicable chronic disease development and has attained menacing global proportions, affecting approximately one of eight adults. Phytochemicals that support energy metabolism and prevent obesity development have been the subject of intense research endeavors over the past several decades. Cycloastragenol is a natural triterpenoid compound and aglycon of astragaloside IV, known for activating telomerase and mitigating cellular aging. Here, we aim to characterize the effect of cycloastragenol on lipid metabolism in a glucose-induced obesity model in Caenorhabditis elegans. We assessed the changes in the body length, width, and area in C. elegans maintained under elevated glucose through automated WormLab system. Lipid accumulation in the presence of either cycloastragenol (100 μM) or orlistat (12 μM), used as a positive anti-obesity control drug, was quantified through Nile Red fluorescent staining. Furthermore, we evaluated the changes in key energy metabolism molecular players in GFP-reporter transgenic strains. Our results revealed that cycloastragenol treatment decreased mean body area and reduced lipid accumulation in the C. elegans glucose-induced model. The mechanistic data indicated that cycloastragenol suppresses the nuclear hormone receptor family member NHR-49 and the delta(9)-fatty-acid desaturase 7 (FAT-7) enzyme, and activates the 5′-AMP-activated protein kinase catalytic subunit alpha-2 (AAK-2) and the protein skinhead 1 (SKN-1) signaling. Collectively, our findings highlight that cycloastragenol reprograms lipid metabolism by down-regulating the insulin-like receptor (daf-2)/phosphatidylinositol 3-kinase (age-1)/NHR-49 signaling while simultaneously enhancing the activity of the AAK-2/NAD-dependent protein deacetylase (SIR-2.1) pathway. The anti-obesogenic potential of cycloastragenol rationalizes further validation in the context of metabolic diseases and obesity management. Full article

Fungal two-component signaling systems comprise histidine kinases (HKs), phosphotransfer intermediates, and response regulators. HKs are classified into eleven groups based on domain architecture; however, Group XI members in Botrytis cinerea remain uncharacterized. In this study, we investigated the functions of two Group XI histidine kinase genes, BcHK71 and BcHK67, in B. cinerea via gene replacement. Phenotypic analysis revealed that BcHK71 and BcHK67 regulate conidiation, infection structures formation, and glycerol synthesis. Notably, BcHK71 maintained cell wall integrity. Both genes also modulated expression of high osmolarity glycerol mitogen-activated protein kinase (HOG-MARK) signaling pathway components (BcYpd1, BcSkn7, BcBos4), while BcHK67 uniquely upregulated BcBrrg1 and enhanced BcHog1 phosphorylation. Transcriptomics analysis further indicated that BcHK71 and BcHK67 participated in pathways related to carbohydrate and lipid transport, metabolism and secondary metabolite biosynthesis. Disruption of these processes reduced pathogenicity and altered fungicide sensitivity in B. cinerea, with the ΔBcHK71 mutant exhibiting more severe pronounced defects. Collectively, our findings underscore the critical roles of BcHK71 and BcHK67 in fungal development and pathogenicity, highlighting their potential as novel targets for controlling fungal diseases and managing fungicide resistance. Full article

Elderly individuals are more vulnerable to disease due to their increased frailty. Emerging evidence highlights the potential of probiotics as geroprotective agents by maintaining gut health and modulating key physiological processes involved in aging, such as inflammation, cognitive functions, and metabolism. Here, we investigated the geroprotective potential of four probiotic strains (Lacticaseibacillus paracasei LPC1114, Limosilactobacillus reuteri PBS072, Bifidobacterium breve BB077, and Bifidobacterium animalis subsp. lactis BL050) using Caenorhabditis elegans as an aging model. Mid-life healthspan parameters were assessed, including lifespan, motility, ROS levels, lipofuscin accumulation, and cognitive capabilities. The probiotics exhibited strain-specific effects. L. reuteri PBS072 and B. lactis BL050 significantly increased locomotion by 20% and decreased ROS levels by 70% and 30% respectively, suggesting enhanced oxidative stress response and neuromuscular maintenance. B. breve BB077, L. paracasei LPC1114, and L. reuteri PBS072 enhanced associative learning performance, whereas B. lactis BL050 improved chemotactic response. Notably, only L. paracasei LPC1114 and L. reuteri PBS072 extended the maximum lifespan by 4 and 5 days, respectively, an effect mediated by the longevity-related genes skn1, sir2.1, and daf16. Our findings highlight the multifaceted, strain-specific geroprotective properties of probiotics and support their potential as microbiome-based interventions to promote healthy aging. Full article

Extracts of Cynanchi Auriculati Radix (RCA), derived from the roots of Cynanchum auriculatum Royle ex Wight. (CA), have been documented to possess anti-inflammatory and antioxidant properties. However, the molecular mechanisms of their anti-aging action remain unclear. The present study aimed to explore the potential anti-aging components and mechanisms of RCA. LC-MS/MS and network pharmacology were used to identify components and targets. In vitro, LPS-induced RAW264.7 macrophages were used to assess anti-inflammatory effects. In vivo, Caenorhabditis elegans models were employed to evaluate lifespan and stress resistance. Five bioactive components were identified. The ethyl acetate extract of RCA (RCAEA) inhibited LPS-induced M1 macrophage polarization by suppressing the expression of NO, PGE2, IL-1β, iNOS, COX-2, TNF-α, and IL-6 via the NF-κB pathway. In C. elegans, RCAEA extended lifespan and enhanced oxidative and heat stress resistance, without affecting reproduction. These benefits were mediated by the PMK-1/SKN-1 pathway, as confirmed using mutant strains. RCAEA is a promising anti-aging and anti-inflammatory agent, acting through NF-κB and PMK-1/SKN-1 signaling pathways. Full article

Diethylhexyl phthalate (DEHP), a common environmental plasticizer, induces oxidative damage and cell apoptosis without efficient treatment. Tremella fuciformis polysaccharides (TFPs) are known natural antioxidants, yet their protection against DEHP toxicity remains unclear. This study aimed to investigate the protective effects of TFP against DEHP-induced toxicity using both human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans models. The results demonstrate that TFPs significantly alleviated DEHP-induced cytotoxicity in HUVECs by reducing reactive oxygen species (ROS) generation and inhibiting mitochondrial apoptosis pathways, which may contribute to the activation of antioxidant systems mediating via Nrf-2. In C. elegans, TFP improved survival rates under DEHP stress and reduced ROS accumulation. This protection was associated with the modulation of the insulin-like pathway and skn-1 gene to increase the expressions of antioxidant genes. Our findings reveal that TFP exhibits protection against DEHP-induced oxidative stress and apoptosis through the synergistic regulation of survival and antioxidant pathways, highlighting its potential as a natural dietary intervention for environmental toxicant-induced health risks. Full article

Scrophularia aestivalis Griseb. is a Balkan endemic species whose phytochemical composition and medicinal properties have not been previously investigated. The therapeutic potential of Scrophularia species has attracted considerable attention, resulting in extensive studies on their chemical and pharmacological properties, with over 200 secondary metabolites identified to date. The present study aimed to explore the phytochemical composition of Bulgarian-origin S. aestivalis, including isolation and characterization of individual secondary metabolites. From methanol extract of the plant’s aerial parts, aucubin, harpagide, 8-O-acetylharpagide, cis- and trans-harpagoside, 6-O-methyl catalpol, acylated derivatives of catalpol, and linarin were isolated and identified. The anti-obesity activity of the extract and primary fractions was evaluated in a Caenorhabditis elegans model of obesity. Significant lipid-reducing activity was demonstrated in four fractions, indicating promising anti-obesogenic properties. Following chemical profiling and quantitative analysis, the main components of the most active fractions were identified, namely the cis- and trans-harpagoside isomers. Subsequent experiments demonstrated that treatment with harpagoside reduced lipid accumulation and improved mitochondrial function in glucose-supplemented worms, with the data suggesting potential involvement of the SKN-1 signaling pathway. Full article

Acorus tatarinowii Schott (A. tatarinowii), a traditional Chinese medicine, has been widely used in the treatment of dementia, particularly AD. α-Asarone is the main active component of A. tatarinowii oil, and its neuroprotective effects and underlying molecular mechanism in AD remain unclear. In this study, we utilized different transgenic Caenorhabditis elegans (C. elegans) AD models to investigate the neuroprotective mechanism of α-asarone in vivo. Our findings revealed that α-asarone significantly ameliorated Aβ- and tau-induced phenotypic abnormalities, including deficits in chemotaxis-related learning, hyposensitivity to exogenous serotonin, and impaired neuronal integrity. Furthermore, the α-asarone treatment effectively reduced Aβ-induced oxidative stress. Mechanistically, α-asarone reduced Aβ accumulation and maintained protein homeostasis by stimulating proteasome degradation and autophagy in an SKN-1/Nrf2-dependent manner. Our study highlights the potential of α-asarone as an SKN-1/Nrf2 activator and its capability to facilitate proteostasis, supporting its therapeutic potential for AD treatment. Full article

Microplastics (MPs) are plastic particles smaller than 5 mm that accumulate in ecosystems and can cause toxicity in organisms by affecting multiple biological processes. This study investigates the effects of poly(methyl methacrylate) microplastic microspheres (MPs, 200 µm diameter) on Caenorhabditis elegans, a widely used model in ecotoxicology. Nematodes were exposed to MPs at concentrations of 0.01, 0.1, 1, and 10 mg/mL, and various toxicological endpoints were assessed. The uptake of MPs was evaluated by µFT-IR analysis. The results indicate that MPs induce a concentration-dependent reduction in body length and alterations in the reproduction rate. Lifespan was also significantly reduced, with a 20% decrease at the highest concentration. Intestinal permeability assays revealed disruption of gut integrity at higher concentrations, and oxidative stress analysis showed a 1.8-fold increase in reactive oxygen species (ROS) levels at 10 mg/mL. Gene expression analysis via real-time qPCR indicated the upregulation of genes involved in oxidative stress and in DNA repair mechanisms. Additionally, the longevity-related transcription factors daf-16 and skn-1 were modulated, suggesting an adaptive stress response. These findings suggest that MPs impair growth, reproduction, and oxidative stress response in C. elegans, emphasizing the potential risks associated with microplastic exposure. Full article