Cai WJ et al. (2008) Zhongguo Zhong Xi Yi Jie He Za Zhi "[Effect of Epimedium flavonoids in retarding aging of C. elegans]"

Huang JH, Cai WJ, Zhang XM

[Zhongguo Zhong Xi Yi Jie He Za Zhi, 2008]

OBJECTIVE: To investigate effect of Epimedium flavonoids (EF), positively controlled by caloric restriction (CR) method, in retarding aging of the model organism C. elegans, in order to establish a basis for studying its action mechanism. METHODS: Experiment for life-time analysis was conducted on animals grouped into the blank group, the CR group, and the high and low dose EF groups to observe their mean lifespan, maximum lifespan and age-dependent mortality. And the reproductive capacity test and acute heat-stress analysis were carried out in the blank group and the high dose EF group to observe the subalgebra and the mean survival time under acute heat-stress at 35 degrees C. RESULTS: As compared with the blank group, the mean lifespan in the two EF group and the maximum lifespan in the high dose EF group were higher, and the age-dependent mortality in the high dose EF group was lower significantly (P<0.05 or P<0.01); as compared with the CR group, the mean lifespan and maximum lifespan in the high dose EF group were higher (P<0.01); but no significant difference of the subalgebra between the blank group and the high dose EF group was shown (P>0.05). Compared with the blank group, the mean lifespan in the high dose EF group was significantly prolonged under acute heat-stress at 35 degrees C (P<0.01). CONCLUSION: EF can retard the aging of C. elegans without damage on the reproductive capacity, and significantly improve its capacity against acute heat-stress.

Cai WJ et al. (2011) PLoS One "Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans."

Wu B, Kapahi P, Huang JH, Zhang XM, Cai WJ, Zhang SQ, Shen ZY

[PLoS One, 2011]

Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and A(1-42) proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.

Werner KM et al. (2014) J Biol Chem "Caenorhabditis elegans recognizes a bacterial quorum-sensing signal molecule through the AWCON neuron."

Semmelhack MF, Bassler BL, Werner KM, Perez LJ, Ghosh R

[J Biol Chem, 2014]

In a process known as quorum sensing, bacteria use chemicals called autoinducers for cell-cell communication. Population-wide detection of autoinducers enables bacteria to orchestrate collective behaviors. In the animal kingdom detection of chemicals is vital for success in locating food, finding hosts, and avoiding predators. This behavior, termed chemotaxis, is especially well studied in the nematode Caenorhabditis elegans. Here we demonstrate that the Vibrio cholerae autoinducer (S)-3-hydroxytridecan-4-one, termed CAI-1, influences chemotaxis in C. elegans. C. elegans prefers V. cholerae that produces CAI-1 over a V. cholerae mutant defective for CAI-1 production. The position of the CAI-1 ketone moiety is the key feature driving CAI-1-directed nematode behavior. CAI-1 is detected by the C. elegans amphid sensory neuron AWC(ON). Laser ablation of the AWC(ON) cell, but not other amphid sensory neurons, abolished chemoattraction to CAI-1. These analyses define the structural features of a bacterial-produced signal and the nematode chemosensory neuron that permit cross-kingdom interaction.

Werner, Kristen et al. (2013) International Worm Meeting "Small Molecule Communication: C. elegans and bacterial chemical signals."

Perez, Lark, Werner, Kristen, Semmelhack, Martin, Bassler, Bonnie

[International Worm Meeting, 2013]

Bacterial group behaviors are governed by a process called quorum sensing, in which bacteria produce, secrete, and detect extracellular signal molecules called autoinducers (AIs). Vibrios produce multiple AIs, some enable intra-species communication and others that promote inter-species communication. Vibrio cholerae produces an intra-species AI called CAI-1 that is a 13 carbon long fatty acyl molecule and the interspecies signal called AI-2 that is a boron-containing furanone. The information contained in the AIs is funneled into a shared phosphorelay signaling cascade that controls virulence, biofilm formation, and other traits. The bacteriovorous nematode, Caenorhabditis elegans, also uses small molecules to interpret its environment. A class of C. elegans-derived molecules called ascarosides influence nematode behaviors including attraction, repulsion, and mating. The presence of bacteria stimulates chemotaxis, egg-laying, and feeding in C. elegans, however, the bacteria-produced molecules that the nematode detects to control these phenotypes are largely unknown. We demonstrate that in addition to playing a vital role in quorum-sensing-regulated behaviors in V. cholerae, CAI-1 also influences behavior in C. elegans. C. elegans is more strongly attracted to V. cholerae than to its food source E. coli HB101 and C. elegans prefers V. cholerae that produces CAI-1 over a V. cholerae mutant for CAI-1 production. Consistent with this finding, robust chemoattraction occurs to synthetic CAI-1. CAI-1 is detected by the sensory neuron AWCON. Laser ablation of this cell, but not other amphid sensory neurons, abolished chemoattraction to CAI-1. To define which moieties of CAI-1 are crucial for recognition by C. elegans, we synthesized CAI-1 analogs and tested whether they promote chemoattraction. The fatty-acid chain length as and the precise position of the CAI-1 ketone group are the key features required for mediating CAI-1-directed nematode behavior. Together, these analyses define a bacteria-produced signal and the nematode detection apparatus that permit interkingdom communication.

Nie LJ et al. (2014) Zhongguo Zhong Xi Yi Jie He Za Zhi "[Effect of compound bushen recipe on chronic fatigue syndrome in C. elegans: an experimental study]."

Cai WJ, Shen ZY, Nie LJ, Zhang XM

[Zhongguo Zhong Xi Yi Jie He Za Zhi, 2014]

OBJECTIVE: To evaluate the effect of compound bushen recipe (CBR) in improving the survival state of stress and the overall life span in C. elegans by simulating chronic fatigue syndrome (CFS) under various stress states. METHODS: The tolerance and the average survival time of adult larvae against heat stress (35 degrees C), oxidative stress (250 microg/mL juglone), and in vivo Abeta protein toxicity (Abeta(1-42) transgenic mutant CL4176) under the intervention of the high (500 mg/L), middle (250 mg/L), and low (100 mg/L) dose CBR were observed. The effect of CBR on the average live time (at 25 degrees C), movement distance in 20 seconds, the frequency of pharyngeal pump in 30 seconds, and the reproductive capability were assessed. RESULTS: Compared with the control group, the survival time of heat stressed C. elegans could be significantly increased in each CBR group (P < 0.01). The survival time of heat stressed C. elegans could be elongated, the protein toxicity be attenuated, and the live time prolonged in the high and middle dose CBR groups (P < 0.01, P < 0.05).The movement distance and the frequency of pharyngeal pump could also be increased in the high dose CBR group (P < 0.01). There was no statistical difference in the reproductive capability among all groups (P > 0.05). CONCLUSIONS: CBR could significantly enhance the stress capacity of C. elegans against internal and external environment, and prolong their lifespan. It did not interfere their normal production, and also could improve the quality of life, thus laying a foundation for further mechanism studies and pharmacological researches on CBR in preventing and treating CFS.

Skora S et al. (2013) EMBO J "Life(span) in balance: oxygen fuels a sophisticated neural network for lifespan homeostasis in C. elegans."

Zimmer M, Skora S

[EMBO J, 2013]

A key finding of modern ageing research is that our limitation in lifespan is more than the result of accumulated organismal decay. Lifespan is regulated by genetically defined chemosensory and endocrine pathways, which integrate signals that reflect the internal and external status of the animal. New findings by Liu and Cai unravel a role for the environmental gases oxygen and carbon dioxide in the regulation of lifespan homeostasis and thus a novel function of oxygen-chemosensory neurons in C. elegans.

Wu JZ et al. (2016) Exp Gerontol "Pyrroloquinoline quinone enhances the resistance to oxidative stress and extends lifespan upon DAF-16 and SKN-1 activities in C. elegans."

Cai WJ, Xia SJ, Khanabdali R, Kalionis B, Wu JZ, Huang JH

[Exp Gerontol, 2016]

Pyrroloquinoline quinone (PQQ) is linked to fundamental biological processes such as mitochondrial biogenesis and lipid metabolism. PQQ may also function as an essential micronutrient during animal development. Recent studies have shown the therapeutic potential of PQQ for several age-related diseases due to its antioxidant capacity. However, whether PQQ can promote longevity is unknown. Here, we investigate the effects of PQQ on oxidative stress resistance as well as lifespan modulation in Caenorhabditis elegans. We find that PQQ enhances resistance to oxidative stress and extends the lifespan of C. elegans at optimal doses. The underlying molecular mechanism involves the increased activities of the primary lifespan extension transcriptional factors DAF-16/FOXO, the conserved oxidative stress-responsive transcription factor SKN-1/Nrf2, and upregulation of daf-16, skn-1 downstream targets including sod-3, hsp16.2, gst-1 and gst-10. Our findings uncover a novel role of PQQ in longevity, supporting PQQ as a possible dietary supplement for overall health improvement.

Zhou YM et al. (2011) Biosci Biotechnol Biochem "An efficient and novel screening model for assessing the bioactivity of extracts against multidrug-resistant Pseudomonas aeruginosa using Caenorhabditis elegans."

Cai WJ, Han LZ, Shao L, Li JA, Chen DJ, Zhou YM, Zhu CB

[Biosci Biotechnol Biochem, 2011]

As a large number of multidrug-resistant bacteria have emerged, and there is an urgent need for the development of new antibacterial agents. In this study, we developed a liquid-based slow killing assay to be carried out in standard 96-well microtiter plates. This screening method was designed to facilitate high-throughput screening of small molecules and extracts. In antibiotic rescue assays, the Caenorhabditis elegans multidrug-resistant Pseudomonas aeruginosa infection model displayed a high degree of drug resistance in vivo and in vitro. We used the method to screen 1,300 extracts, and found 36 extracts (2.7%) which prolonged the survival of infected nematodes, and four (0.3%) of these extracts showed in vitro and in vivo anti-multidrug resistant P. aeruginosa activity. These results indicate that the whole-animal C. elegans multidrug-resistant bacterial model can be used to screen antibacterial compounds, and can also be useful for bioactive compounds which most likely cannot be identified in vitro.

Chisnell P et al. (2018) MicroPubl Biol "Silencing the ASI gustatory neuron pair extends lifespan"

Kenyon C, Chisnell P

[MicroPubl Biol, 2018]

Disrupting the function of sensory neurons of C. elegans can increase their lifespan (Apeld and Kenyon 1999). This effect is not limited to large-scale disruption, as ablation of single pairs of neurons have been shown to modify lifespan (Alcedo and Kenyon 2004; Lee and Kenyon 2009; Liu and Cai 2013). We tested whether silencing the neuron pair ASI with the tetanus toxin light chain (Tetx), as opposed to ablating it, could increase lifespan. Tetanus toxin disrupts neurotransmission by blocking the release of both small clear-core vesicles and large dense-core vesicles, but should not affect communication via gap junctions (Schiavo et al. 1992; McMahon et al. 1992). We expressed GFP::Tetx using the ASI-specific promoter pgpa-4 (Figure Panel A) and conducted lifespan assays comparing animals with high fluorescence and undetectable fluorescence. Tetx in ASI extended lifespan in otherwise wild-type animals (Figure Panel B, Table 1, 14.9% average median lifespan increase across 5 replicates).

Redemann, Stefanie et al. (2010) C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany "Codon adaptation-based control of protein expression levels in C. elegans and its application to GPR-1 allows control of microtubule-based pulling force"

Redemann, Stefanie, Ernst, Susanne, Ayloo, Swathi, Bringmann, Henrik, Schloissnig, Siegfried, Pozniakowski, Andrej, Hyman, Anthony A

[C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany, 2010]

The variation of the expression level of a protein could provide a powerful tool to study protein function. However, there is no method that allows the precise control of protein levels under a native promotor in eukaryotes. We developed a method, which enables us to fine tune the protein expression levels in C. elegans by using synthetic genes with adapted codons. By modifying the codon usage of a gene, the Codon adaptation index (CAI) can be changed and the level of protein expression can be controlled. We used this method to regulate the expression of the G-protein regulator GPR-1/2, which is involved in force generation during spindle positioning in the first asymmetric cell division in C. elegans. By gradually increasing the amount of GPR-1/2, we found that the amount of force acting on the spindle in C. elegans embryos is directly related to the amount of the G protein regulator GPR1/2 in the cell. In C. elegans GPR-1/2 is found in a complex, the force-generating complex,which is thought to consist of at least three proteins: GPR-1/2, LIN-5 and a G-alpha protein. Since increasing the amount of GPR1/2 is sufficient to increase the force, this suggests that the other proteins are there in excess and that GPR-1/2 is the limiting component. The modification of the CAI is a good example of how the ability to over-express proteins is essential for identifying components that are limiting as opposed to permissive for force generation. This method provides the first way to control the level of protein expression levels in C. elegans, and the first method for overexpression of proteins in the C. elegans germline. With this method the protein levels of a protein of interest can be varied, while maintaining all the wild type genetic regulation and the wild type protein sequence.