C. elegans: a prominent platform for modeling and drug screening in neurological disorders.

INTRODUCTION: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience. AREAS COVERED: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states. EXPERT OPINION: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.

Aquilaria crassna Leaf Extract Ameliorates Glucose-Induced Neurotoxicity In Vitro and Improves Lifespan in Caenorhabditis elegans.

Hyperglycemia is one of the important causes of neurodegenerative disorders and aging. Aquilaria crassna Pierre ex Lec (AC) has been widely used to relieve various health ailments. However, the neuroprotective and anti-aging effects against high glucose induction have not been investigated. This study aimed to investigate the effects of hexane extract of AC leaves (ACH) in vitro using human neuroblastoma SH-SY5Y cells and in vivo using nematode Caenorhabditis elegans. SH-SY5Y cells and C. elegans were pre-exposed with high glucose, followed by ACH treatment. To investigate neuroprotective activities, neurite outgrowth and cell cycle progression were determined in SH-SY5Y cells. In addition, C. elegans was used to determine ACH effects on antioxidant activity, longevity, and healthspan. In addition, ACH phytochemicals were analyzed and the possible active compounds were identified using a molecular docking study. ACH exerted neuroprotective effects by inducing neurite outgrowth via upregulating growth-associated protein 43 and teneurin-4 expression and normalizing cell cycle progression through the regulation of cyclin D1 and SIRT1 expression. Furthermore, ACH prolonged lifespan, improved body size, body length, and brood size, and reduced intracellular ROS accumulation in high glucose-induced C. elegans via the activation of gene expression in the DAF-16/FoxO pathway. Finally, phytochemicals of ACH were analyzed and revealed that ß-sitosterol and stigmasterol were the possible active constituents in inhibiting insulin-like growth factor 1 receptor (IGFR). The results of this study establish ACH as an alternative medicine to defend against high glucose effects on neurotoxicity and aging.

Hydroalcoholic extract of Haematoxylum brasiletto protects Caenorhabditis elegans from cadmium-induced toxicity.

BACKGROUND: H. brasiletto is used in popular culture due to its therapeutic properties, including antioxidant, anti-inflammatory and antiproliferative properties, although little is known about its role as a protector against metal toxicity. This study aimed to investigate the chemical composition and efficacy of the hydroalcoholic extract from H. brasiletto (HAE-Hbrasiletto) collected in northern Colombia to defend against cadmium (Cd)-induced toxicity. METHODS: Phytochemical characterization was performed using HPLC-ESI-QTOF. Caenorhabditis elegans was employed to assess the shielding effect of HAE-Hbrasiletto against Cd toxicity in vivo, and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was utilized to measure radical scavenging activity. RESULTS: The main secondary metabolites identified by HPLC-ESI-QTOF in the extracts were hematoxylins (brazilein and hematein) and protosappanins (protosappanin A, B and C, 10-O-methylprotosappanin B, and protosappanin A dimethyl acetal). The HAE-Hbrasiletto elicited low lethality in N2 worms and significantly reduced the Cd-induced death of the nematodes. It also improved Cd-induced motility inhibition, as well as body length and reproduction reduction provoked by the heavy metal. The extract displayed a good capacity to halt Cd-induced DAF-16 translocation. As this last process was associated with lethality (r = 0.962, p < 0.01), the antioxidant properties of the extract may contribute to ameliorating tissue damage induced by oxidative stress from Cd exposure. CONCLUSION: HAE-Hbrasiletto has remarkable properties to protect against Cd-induced toxicity.

Orientin Prolongs the Longevity of Caenorhabditis elegans and Postpones the Development of Neurodegenerative Diseases via Nutrition Sensing and Cellular Protective Pathways.

Age is the major risk factor for most of the deadliest diseases. Developing small molecule drugs with antiaging effects could improve the health of aged people and retard the onset and progress of aging-associated disorders. Bioactive secondary metabolites from medicinal plants are the main source for development of medication. Orientin is a water-soluble flavonoid monomer compound widely found in many medicinal plants. Orientin inhibits fat production, antioxidation, and anti-inflammatory activities. In this study, we explored whether orientin could affect the aging of C. elegans. We found that orientin improved heat, oxidative, and pathogenic stress resistances through activating stress responses, including HSF-1-mediated heat shock response, SKN-1-mediated xenobiotic and oxidation response, mitochondria unfolded responses, endoplasmic unfolded protein response, and increased autophagy activity. Orientin also could activate key regulators of the nutrient sensing pathway, including AMPK and insulin downstream transcription factor FOXO/DAF-16 to further improve the cellular health status. The above effects of orientin reduced the accumulation of toxic proteins (α-synuclein, ß-amyloid, and poly-Q) and delayed the onset of neurodegenerative disorders in AD, PD, and HD models of C. elegans and finally increased the longevity and health span of C. elegans. Our results suggest that orientin has promising antiaging effects and could be a potential natural source for developing novel therapeutic drugs for aging and its related diseases.

The rice bran peptide KF-8 extends the lifespan and improves the healthspan of Caenorhabditis elegans via skn-1 and daf-16.

With the increased aging of the population, the extension of lifespan and the improvement of healthspan have become important. Our previous studies showed that the rice bran peptide KF-8 exerts an antioxidant effect in cells and mice. In this study, we evaluated the effects of KF-8 on the healthspan and lifespan of Caenorhabditis elegans. We found that KF-8 prolonged the life of nematodes and showed no reproductive toxicity towards nematodes. In addition, KF-8 improved the motility of nematodes and resulted in an extended body length. Using hydrogen peroxide and juglone as stress inducers, we found that KF-8 improved the anti-stress ability of nematodes. In addition, KF-8 upregulated the expressions of skn-1, daf-16 and antioxidant genes. In addition, the life-prolonging effect of KF-8 was lost in skn-1 mutant strains and daf-16 mutant strains, indicating that KF-8 may exert anti-aging effects through skn-1 and daf-16.

A Lycium barbarum extract inhibits ß-amyloid toxicity by activating the antioxidant system and mtUPR in a Caenorhabditis elegans model of Alzheimer's disease.

Lycium barbarum, a traditional Chinese medicine, has been shown to have antioxidant properties and has a protective effect in many diseases related to oxidative stress, such as neurodegenerative diseases, cardiovascular diseases, and cancer. Although the neuroprotective effects of L. barbarum extract (LBE) have been reported in several studies, the underlying molecular mechanisms are still unclear. In this study, the transgenic Caenorhabditis elegans strain CL2006 was used to investigate the function and molecular mechanism of an LBE in Alzheimer's disease (AD). LBE had high antioxidant potential and effectively delayed Aß-induced paralysis in the CL2006 strain. LBE inhibited the production of excessive reactive oxygen species by inducing the SKN-1-mediated antioxidant system, thereby inhibiting the generation of Aß and inhibiting mitochondrial damage. Importantly, LBE reduced Aß levels by inducing FSHR-1-mediated activation of the mtUPR. Therefore, our study not only reveals a new mechanism of LBE in the treatment of AD but also identifies a novel strategy for the treatment of AD by enhancing the mtUPR.

Adaptive capacity to dietary Vitamin B12 levels is maintained by a gene-diet interaction that ensures optimal life span.

Diet regulates complex life-history traits such as longevity. For optimal lifespan, organisms employ intricate adaptive mechanisms whose molecular underpinnings are less known. We show that Caenorhabditis elegans FLR-4 kinase prevents lifespan differentials on the bacterial diet having higher Vitamin B12 levels. The flr-4 mutants are more responsive to the higher B12 levels of Escherichia coli HT115 diet, and consequently, have enhanced flux through the one-carbon cycle. Mechanistically, a higher level of B12 transcriptionally downregulates the phosphoethanolamine methyltransferase pmt-2 gene, which modulates phosphatidylcholine (PC) levels. Pmt-2 downregulation activates cytoprotective gene expression through the p38-MAPK pathway, leading to increased lifespan only in the mutant. Evidently, preventing bacterial B12 uptake or inhibiting one-carbon metabolism reverses all the above phenotypes. Conversely, supplementation of B12 to E. coli OP50 or genetically reducing PC levels in the OP50-fed mutant extends lifespan. Together, we reveal how worms maintain adaptive capacity to diets having varying micronutrient content to ensure a normal lifespan.

Eugenol Elicits Prolongevity by Increasing Resistance to Oxidative Stress in C. elegans.

AIMS: To analyze the efficacy of eugenol on longevity by assessing its antioxidant effect using Caenorhabditis elegans as an animal model. BACKGROUND: Eugenol is a major polyphenolic component of Ocimum sanctum (Tulsi) which attributes wide pharmacological activities and can serve as a biomarker. However, the possible effect of eugenol on longevity in Caenorhabditis elegans has not been reported. OBJECTIVE: The objective of this investigation was to provide the first scientific based results about the effect of eugenol on longevity, slowing down of paralysis in Alzheimer's model and the mechanism behind it in Caenorhabditis elegans animal model system. METHODS: The phenolic components of methanolic extract of Ocimum sanctum were analyzed by RP-HPLC. Worms were exposed to different concentrations of extract and one of its components - eugenol. Lifespan, health span, survival in CL4176 Alzheimer's model and molecular mechanism were analyzed. RESULTS: Extract of Ocimum sanctum and eugenol increased lifespan and provided indemnity against pro-oxidants. It also significantly improved healthy ageing and slowed the progression of neurodegeneration in CL4176 Alzheimer's model of the worm by increasing survival against prooxidants and slowing down the paralysis. Longevity effect was independent of the DAF-16 as observed by using DAF-16::GFP and daf-16 null mutant strains. These results implicate eugenol as a potent therapeutic compound that may curtail ageing and age related disorders like- Alzheimer's disease. CONCLUSION: The present work demonstrated eugenol as a potential anti-ageing compound that may curtail ageing, improve heath span by enhancing resistance to oxidative stress and exerts its effect independent of DAF-16 pathway. So, it can be assumed that eugenol can be beneficial to humans as well, albeit further research is necessary before declaring it for human consumption.

Isolation and characterisation of nematicidal compound, leolorin C, from Leonotis leonurus acetone leaf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonotis leonurus (L.) R.Br. (Lamiaceae) is a perennial shrub native to South Africa used to treat various diseases including digestive tract problems, intestinal worms and constipation. AIM OF THE STUDY: The aim was to isolate and characterise nematicidal compounds from leaves of L. leonurus. MATERIALS AND METHODS: Bioassay-guided fractionation was carried out using the free-living nematode Caenorhabditis elegans as a model organism. Structural elucidation of the purified compound was carried out using NMR spectroscopic analyses and UPLC-QTOF-MS. The fractions and the isolated compound were tested for nematicidal activity on motility of plant-parasitic Meloidogyne incognita juveniles (J2s) and J2 hatch inhibition. Further screening was done to determine the minimum inhibitory concentration (MIC) of the fractions against bacterial phytopathogens and cytotoxicity against Vero kidney cells. RESULTS: Leoleorin C isolated from L. leonurus had moderate activity against C. elegans juveniles (34%) but was not active against J2 motility and J2 hatch of M. incognita. Thus, activity against the free-living C. elegans did not correspond with efficacy against plant-parasitic nematodes. Leoleorin C was not active against the tested bacterial phytopathogens, but some activity was observed in the bioautography assay against Clavibacter michiganensis subsp. michiganensis, the organism causing bacterial canker in tomatoes. The plant extract, fractions and leolorin C were relatively non-toxic to Vero cells with LC50 values greater than 0.01 mg/mL. CONCLUSION: The crude extract of L. leonurus and fractions may be useful in developing complementary treatments for controlling nematodes and phytopathogens. This study does not support the use of free-living nematodes as a model to isolate anti-parasitic compounds from plants.

Anthelmintic Activity and Cytotoxic Effects of Compounds Isolated from the Fruits of Ozoroa insignis Del. (Anacardiaceae).

Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1-3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds.

Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems.

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer's disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses ß-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

Non-Woven Infection Prevention Fabrics Coated with Biobased Cranberry Extracts Inactivate Enveloped Viruses Such as SARS-CoV-2 and Multidrug-Resistant Bacteria.

The Coronavirus Disease (COVID-19) pandemic is demanding the rapid action of the authorities and scientific community in order to find new antimicrobial solutions that could inactivate the pathogen SARS-CoV-2 that causes this disease. Gram-positive bacteria contribute to severe pneumonia associated with COVID-19, and their resistance to antibiotics is exponentially increasing. In this regard, non-woven fabrics are currently used for the fabrication of infection prevention clothing such as face masks, caps, scrubs, shirts, trousers, disposable gowns, overalls, hoods, aprons and shoe covers as protective tools against viral and bacterial infections. However, these non-woven fabrics are made of materials that do not exhibit intrinsic antimicrobial activity. Thus, we have here developed non-woven fabrics with antimicrobial coatings of cranberry extracts capable of inactivating enveloped viruses such as SARS-CoV-2 and the bacteriophage phi 6 (about 99% of viral inactivation in 1 min of viral contact), and two multidrug-resistant bacteria: the methicillin-resistant Staphylococcus aureus and the methicillin-resistant Staphylococcus epidermidis. The morphology, thermal and mechanical properties of the produced filters were characterized by optical and electron microscopy, differential scanning calorimetry, thermogravimetry and dynamic mechanical thermal analysis. The non-toxicity of these advanced technologies was ensured using a Caenorhabditis elegans in vivo model. These results open up a new prevention path using natural and biodegradable compounds for the fabrication of infection prevention clothing in the current COVID-19 pandemic and microbial resistant era.

Ginkgo seed extract promotes longevity and stress resistance of Caenorhabditis elegans.

Ginkgo seeds are a traditional food in China valued for their nutritional and health benefits. However, little is known about the anti-aging and health-promoting effects of ginkgo seed products. Here, we showed that ginkgo seed powder extract (GSP-E) is abundant in alkaloids and flavonoids, and can extend the lifespan of Caenorhabditis elegans. GSP-E improved most physiological indicators related to aging of C. elegans, including locomotor activity, reproductive capacity, and resistance to oxidation and heat. Moreover, GSP-E reduced the accumulation of lipofuscin and reactive oxygen species (ROS) in C. elegans. Further studies demonstrated that GSP-E improved longevity and stress resistance by mediating lipid metabolism and autophagy, as well as by regulating gene expression (e.g., FASN-1, POD-2, GPX-7, FAT-5). GSP-E has an anti-amyloid effect and delayed amyloid-induced paralysis of C. elegans. These findings could support the utilization of ginkgo seed as a potential dietary supplement for the health food industry, and provide a novel health-promoting resource against aging and aging-related diseases.

Anti-aging effects of the fermented anthocyanin extracts of purple sweet potato on Caenorhabditis elegans.

Anthocyanins have anti-inflammatory, anticarcinogenic and antioxidant properties and anti-aging effects as well as potential application as pigments. The metabolism of anthocyanins in fermented food has attracted increasing attention. However, the effect of lactic acid bacteria (LAB) fermentation on its anti-aging activity remains mostly unknown. The current study aimed to investigate the compositions, antioxidant activities and anti-aging effect of fermented purple sweet potato anthocyanins (FSPA) on aging Caenorhabditis elegans compared to raw purple sweet potato anthocyanins (PSPA). Results showed that anthocyanins were degraded into more bioavailable phenolic acids by Weissella confusa fermentation. PSPA and FSPA can extend the lifespan of C. elegans by 26.7% and 37.5%, respectively, through improving the activity of antioxidant enzymes as well as decreasing MDA content, ROS levels and lipofuscin accumulation. Pretreatment of the worms with PSPA and FSPA induced their potential to resist to thermal tolerance and oxidative stress, and FSPA exerted a higher anti-stress effect than PSPA. Moreover, FSPA supplementation upregulated the mRNA expressions of genes daf-16, hsp-16.2, sir-2.1, skn-1 and sod-3 and downregulated the expression of daf-2 in the nematodes, whereas PSPA only induced the increase in the expressions of sir-2.1, skn-1 and sod-3. Overall, FSPA can improve stress resistance and extend the lifespan of C. elegans by both insulin/IGF-1 signaling pathway and dietary restriction pathway, providing a theoretical basis for the application of PSPA in fermented food as functional pigments.

Trigonelline Extends the Lifespan of C. Elegans and Delays the Progression of Age-Related Diseases by Activating AMPK, DAF-16, and HSF-1.

Trigonelline is the main alkaloid with bioactivity presented in fenugreek, which was used in traditional medicine in Asian countries for centuries. It is reported that trigonelline has anti-inflammatory, anti-oxidant, and anti-pathogenic effects. We are wondering whether trigonelline have anti-aging effect. We found that 50 µM of trigonelline had the best anti-aging activity and could prolong the lifespan of Caenorhabditis elegans (C. elegans) by about 17.9%. Trigonelline can enhance the oxidative, heat, and pathogenic stress resistance of C. elegans. Trigonelline could also delay the development of neurodegenerative diseases, such as AD, PD, and HD, in models of C. elegans. Trigonelline could not prolong the lifespan of long-lived worms with loss-of-function mutations in genes regulating energy and nutrition, such as clk-1, isp-1, eat-2, and rsks-1. Trigonelline requires daf-16, hsf-1, and aak-2 to extend the lifespan of C. elegans. Trigonelline can also up-regulate the expression of daf-16 and hsf-1 targeted downstream genes, such as sod-3, gst-4, hsp-16.1, and hsp-12.6. Our results can be the basis for developing trigonelline-rich products with health benefits, as well as for further research on the pharmacological usage of trigonelline.

Ginsenoside Prolongs the Lifespan of C. elegans via Lipid Metabolism and Activating the Stress Response Signaling Pathway.

Panax ginseng is a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides from Panax ginseng, on the lifespan of Caenorhabditis elegans (C. elegans). We found that TG extended the lifespan of C. elegans and reduced lipofuscin accumulation. Moreover, TG increased the survival of C. elegans in response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression of nrh-80, daf-12, daf-16, hsf-1 and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan of daf-16 and hsf-1 mutants, highlighting their role in the antiaging effects of TG in C. elegans. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg1, Rg2 and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan of C. elegans to levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside in C. elegans.

Polygonum multiflorum Thunb extract extended the lifespan and healthspan of Caenorhabditis elegans via DAF-16/SIR-2.1/SKN-1.

Polygonum multiflorum Thunb (PMT), as a traditional Chinese herbal medicine, has been widely used in the prevention and treatment of aging-related diseases, including Alzheimer's disease, Parkinson's disease, hyperlipidemia, atherosclerosis and inflammation. However, the effect of PMT on the lifespan and its molecular mechanisms are still unclear. Here we found that 60% ethanol refined fraction (PMT-E) of Polygonum multiflorum Thunb at 50 µg mL-1, which contained two main bioactive compounds, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and emodin-8-O-ß-D-glucoside (EG), could significantly increase the mean lifespan by 19.82%, delay the age-related decline of phenotypes, enhance stress resistance and reduce ROS accumulation in Caenorhabditis elegans. Moreover, we also found that the mitochondrial membrane potential (ΔΨ) and ATP content of worms treated with 50 µg mL-1 PMT-E were obviously improved. Further mechanistic studies revealed that DAF-16, SIR-2.1 and SKN-1 transcription factors were required for PMT-E-mediated lifespan extension. Finally, we found that PMT-E could significantly inhibit the toxicity induced by ß-amyloid (Aß) in Aß transgenic worms. Altogether, these findings laid the foundation for the use of Polygonum multiflorum Thunb to treat aging and age-related diseases.

Youthful and age-related matreotypes predict drugs promoting longevity.

The identification and validation of drugs that promote health during aging ("geroprotectors") are key to the retardation or prevention of chronic age-related diseases. Here, we found that most of the established pro-longevity compounds shown to extend lifespan in model organisms also alter extracellular matrix gene expression (i.e., matrisome) in human cell lines. To harness this observation, we used age-stratified human transcriptomes to define the age-related matreotype, which represents the matrisome gene expression pattern associated with age. Using a "youthful" matreotype, we screened in silico for geroprotective drug candidates. To validate drug candidates, we developed a novel tool using prolonged collagen expression as a non-invasive and in-vivo surrogate marker for Caenorhabditis elegans longevity. With this reporter, we were able to eliminate false-positive drug candidates and determine the appropriate dose for extending the lifespan of C. elegans. We improved drug uptake for one of our predicted compounds, genistein, and reconciled previous contradictory reports of its effects on longevity. We identified and validated new compounds, tretinoin, chondroitin sulfate, and hyaluronic acid, for their ability to restore age-related decline of collagen homeostasis and increase lifespan. Thus, our innovative drug screening approach-employing extracellular matrix homeostasis-facilitates the discovery of pharmacological interventions promoting healthy aging.

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.

HSF-1 and SIR-2.1 linked insulin-like signaling is involved in goji berry (Lycium spp.) extracts promoting lifespan extension of Caenorhabditis elegans.

The anti-cancer, vision-improving, and reproduction-enhancing effects of goji berry have been generally recognized, but its role in anti-aging is rarely studied in depth. Therefore, two widely-circulated goji berries, Lycium ruthenicum Murr. (LRM) and Lycium Barbarum. L (LB), were selected to explore their effects on extending lifespan and enhancing defense against extrinsic stress and to uncover the mechanism of action through genetic study. The results showed that supplementation with high-dose LRM (10 mg mL-1) and LB (100 mg mL-1) extracts significantly extended the lifespan of Caenorhabditis elegans (C. elegans) by 25.19% and 51.38%, respectively, accompanied by the improved stress tolerance of C. elegans to paraquat-induced oxidation, UV-B irradiation and heat shock. Furthermore, LRM and LB extracts remarkably enhanced the activities of antioxidant enzymes including SOD and CAT in C. elegans, while notably decreased the lipofuscin level. Further genetic research demonstrated that the expression levels of key genes daf-16, sod-2, sod-3, sir-2.1 and hsp-16.2 in C. elegans were up-regulated by the intervention with LRM and LB, while that of the age-1 level was down-regulated. Moreover, the daf-16 (mu86) I, sir-2.1 (ok434) IV and hsf-1 (sy441) I mutants reversed the longevity effect brought about by LRM or LB, which confirmed that these genes were required in goji berry-mediated lifespan extension. Therefore, we conclude that HSF-1 and SIR-2.1 act collaboratively with the insulin/IGF signaling pathway (IIS) in a daf-16-independent mode. The present study indicated goji berry as a potential functional food to alleviate the symptoms of aging.