Bakaev VV (1997) Worm Breeder's Gazette "AN ATTEMPT TO SLOW AGING IN C. elegans. 6. NO EFFECT OF ROYAL JELLY EXTRACT WATER SOLUION IN CONCENTRATION 1:100,000,000"

Bakaev VV

[Worm Breeder's Gazette, 1997]

In this investigation nematodes C. elegans lived in liquid me- dium with E. coli and water solution of royal jelly extract in concentration 1:100 000 000 in order to study its effect on longevity of these worms in comparison with control, where ne- matodes lived without this extract. Three adult animals (3 - 5 days old) were kept in microtitre wells containing 0,75 ml of liquid medium (with E. coli and without royal jelly extract) during 4 hours, then they were discarded and newborn larvae we- re transferred in next wells (with royal jelly extract in any concentration) every day (one worm in one well). This investi- gation was carried out in room temperature and in the dark- ness. The obtained results were as follows (mean and standard error): Control group Experimental group Longevity (in days) Mean 17,19 +/- 1,03 16,31 +/- 1,08 Maximal 29 30 Minimal 8 7 Number of animals 36 35 Conclusion: The water solution of royal jelly extract has no effect on C. elegans longevity.

Bakaev VV (1996) Worm Breeder's Gazette "AN ATTEMPT TO SLOW AGING IN C. elegans. 5. THE EFFECT OF ROYAL JELLY EXTRACT WATER SOLUTIONS IN DIFFERENT CONCENTRATIONS"

Bakaev VV

[Worm Breeder's Gazette, 1996]

The purpose of this study was the effect of different concentrations of royal jelly extract on nematode life span. In this experiment royal jelly extract was used in the form of "Apilactosa" (produced by "Fertane", Moscow, Nagatinskaya str., 1) in following dilutions 1:10*3, 1:10*4, 1:10*5, 1:10*6 , 1:10*7 , 1:10*8 , 1:10*9 and 1:10*10. Three adult animals (3 - 5 days old) were kept in microtitre wells containing 0,75 ml of liquid medium (with E. coli and without royal jelly extract) during 4 hours, then they were discarded and newborn larvae were transferred in next wells (with royal jelly extract in any concentration) every day (one worm in one well). This investigation was carried out in temperature +21C and in the darkness. The obtained results are presented in the following table. Concentration of royal Longevity jelly extract n mean +/- S.D. maximal 1:10*3 12 Lethal 1:10*4 11 18,2 +/- 1,8 28 1:10*5 12 19,2 +/- 2,2 32 1:10*6 12 19,3 +/- 1,7 28 1:10*7 12 15,8 +/- 2,2 28 1:10*8 11 20,6 +/- 3,1 32 1:10*9 8 12,3 +/- 3,5 34 1:10*10 12 17,5 +/- 2,3 31 Conclusion: If the extract from royal jelly was applied to C. elegans during the whole life span in above described conditions, the most effective concentration was 1:10*8. It seemed for me more reasonable to study the effect on longevity of any concentrations near 1:10*8. Acknowledgment: The author wishes to express his thanks to CGC for providing C. elegans (Bristol, N2) and E. coli OP50.

Burke, Daniel et al. (2013) International Worm Meeting "Worms That Exercise Age Better."

Driscoll, Monica, Burke, Daniel, Gefter, Leo, Chang, Christina, Royal, Mary Anne

[International Worm Meeting, 2013]

Exercise has been identified as a powerful maintenance promoter, with anti-cancer, anti-diabetes, anti-sarcopenia, anti-cognitive decline, and possibly pro-immune consequences in humans. Nonetheless, the molecular, cellular, and systems-wide changes by which exercise extends healthspan remain poorly understood, limiting exploitation of molecular exercise pathways for therapeutic application. We have developed a swim training regimen for the nematode Caenorhabditis elegans. Adult and juvenile worms "exercised" by swimming in M9 on successive days exhibit an exercise benefit, as measured by CELEST swimming analysis software developed by Dr. C. Restif together with the Driscoll lab. We show that like in mammals, exercise can increase physical performance after repeat training, exercise benefits diminish if training is stopped, and too much exercise is deleterious. Importantly, two independent mutants for aak-2, a conserved subunit of an AMP kinase homologue that acts upstream of the transcriptional activator PGC-1a to increase mitochondrial density in response to physical activity in higher organisms, do not gain a training benefit, even though they swim train like wild type worms. We have also found that increased mitochondrial biogenesis is associated with improved swimming prowess. Our data suggest that molecular mechanisms by which C. elegans gain an exercise benefit may be conserved from nematodes to humans. Interestingly, animals that exercise exhibit some systemic health benefits such as extended period of pharyngeal pumping and longer median lifespans. In sum, our results suggest that C. elegans can be used as a model system for elucidating the molecular, cellular, and systems-wide benefits that occur as a consequence of exercise.

Maine EM et al. (1994) Worm Breeder's Gazette "Mutations That Enhance glp-1 Identify Genes Required For Various Aspects of Germline Development."

Gelber MB, Smardon AM, Shu P, Qiao L, Maine EM, Lissemore JL

[Worm Breeder's Gazette, 1994]

Mutations that enhance glp-1 identify genes required for various aspects of germline development. Eleanor Maine, Li Qiao, Jim Lissemore-, Pei Shu, Anne Smardon, and Melanie Gelber. Biology Dept., Syracuse University, Syracuse, NY 13244 and Biology Dept., John Carroll University, Cleveland, OH 44118.

Bakaev VV (1996) Worm Breeder's Gazette "AN ATTEMPT TO SLOW AGING IN C. elegans. 4. THE EFFECT OF EXTRACT FROM ROYAL JELLY DURING PREREPRODUCTIVE PERIOD"

Bakaev VV

[Worm Breeder's Gazette, 1996]

It is well known that the royal jelly markedly prolongs the life span of honey bees. This substance is recommended by physicians for increasing of life quality. In this experiment royal jelly extract was used in the form of "Apilac" in dilutions 0,02% and 0,002%. The medium for control group was prepared by mixing S medium containing E. coli with S medium without E. coli (1:1). Three adult animals (3 - 5 days old) were kept in microtitre wells containing 0,75 ml of liquid medium (with E. coli and with or without royal jelly extract) during 6 hours, then they were discarded and newborn larvae were transferred in next wells every day (one worm in one well). Beginning from third day in the whole experiment was used the medium without this royal jelly extract. A number of progeny was calculated every day. This investigation was carried out in temperature +21C and in the darkness. The obtained results are presented in the following table. Control group Experimental Experimental group (0,02%) group (0,002%) n = 11 n = 11 n = 12 Mean +/- S.D. Mean +/- S.D. Mean +/- S.D Longevity (days): mean 19,4 +/- 1,2 18,0 +/- 1,7 21,8 +/- 1,2 maximal 25 27 26 minimal 10 9 14 Periods (days): prereproductive 2 2 2 reproductive 6,5 +/- 0,5 7,4 +/- 0,6 5,9 +/- 0,4 postreproductive 10,6 +/- 1,2 8,5 +/- 1,6 14,0 +/- 1,3 Fecundity: mean 158,8 +/- 6,6 93,9 +/- 9,9 128,9 +/- 3,4 maximal 197 179 153 minimal 115 60 111

Laranjeiro, Ricardo et al. (2015) International Worm Meeting "Benefits of physical exercise to healthy aging in C. elegans."

Chang, Christina, Burke, Daniel, Vanapalli, Siva A., Royal, Mary Anne, Rahman, Mizanur, Yu, Tianyi, Laranjeiro, Ricardo, Driscoll, Monica

[International Worm Meeting, 2015]

Physical exercise is the most efficient and accessible intervention that can promote healthy aging in humans. In fact, exercise has been reported to prevent, or improve consequences of, a wide range of conditions, such as diabetes, cancer, sarcopenia, cardiovascular disease, and neurodegenerative diseases. However, the molecular mechanisms by which exercise can confer systemic health benefits remain largely unknown.We developed novel exercise training protocols for both juvenile and adult C. elegans based on regular swimming regimens. Exercise-trained animals exhibit a swim performance improvement. Furthermore, we developed a microfluidic device with deformable micro-pillars that can directly measure the force an animal is able to exert ('Nemaflex'), and have made considerable progress on automation of data analysis. Our Nemaflex quantitation reveals that exercise-trained animals can exert significantly higher forces than their untrained counterparts. This direct readout of muscle performance shows that our protocols lead to relevant physiological changes in C. elegans. Animals that just sit in the pool such as those temporarily paralyzed by levamisole do not exhibit training adaptations in strength. Thus, animals must swim to get stronger and the simple exposure to liquid does not confer strength adaptations. We find that two central mediators of exercise signaling in mammals - AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK) - are also essential for the muscle exercise benefits observed in C. elegans (aak-2 and pmk-1, respectively). Moreover, mutation of a repressor of mitochondrial function (NCoR1/gei-8) in C. elegans leads to an increased muscle performance even without exercise training ('natural athlete'). These results show that the major exercise signaling mechanisms are conserved from nematodes to humans, making C. elegans an ideal model to dissect the genetic regulation of exercise systemic health benefits. Other than muscle improvement, our swimming protocols in C. elegans promote physiological changes in other tissues (e.g., neurons and pharynx) throughout the aging process. Careful characterization of these systemic benefits of exercise in C. elegans may provide novel insight into critical mechanisms for functional maintenance late into life.

(2019) Development "The people behind the papers - Julia Brandt, Mary Rossillo and Niels Ringstad."

[Development, 2019]

A fundamental aim in developmental biology is to understand how the various cell types of the body are specified by differential gene regulation. <i>Caenorhabditis</i><i>elegans</i> nervous system development provides a powerful system for studying this, as exemplified by a new Development paper reporting on how the BAG neurons that help the worm sense oxygen and carbon dioxide are specified. We caught up with first authors Julia Brandt and Mary Rossillo and their supervisor Niels Ringstad (Associate Professor at the Skirball Institute of Biomolecular Medicine and Department of Cell Biology at New York University) to find out more about the story.

Detienne G et al. (2014) Exp Gerontol "Royalactin extends lifespan of Caenorhabditis elegans through epidermal growth factor signaling."

Schoofs L, Ernst UR, Detienne G, Temmerman L, De Haes W

[Exp Gerontol, 2014]

Royalactin is a glycoprotein essential for the development of long-lived queen honeybees. Only larvae fed with royal jelly, containing royalactin, develop into queens. Royalactin plays a central role in this process by switching on the epidermal growth factor (EGF) receptor signaling pathway which ultimately leads to epigenetic changes and a long-lived queen phenotype. Recently it was shown that royalactin by itself also extends lifespan in Drosophila melanogaster. Yet, the mechanism by which royalactin promotes longevity remains largely unknown. We set out to characterize the effects of royalactin on Caenorhabditis elegans lifespan, and clarify the possible involvement of EGF signaling in this process. We demonstrate that royalactin extends lifespan of this nematode and that both EGF (LIN-3) and its receptor (LET-23) are essential to this process. To our knowledge, this is the first report of royalactin-mediated lifespan extension in a non-insect species. Additionally, we show that royalactin enhances locomotion in adult nematodes, implying that royalactin also influences healthspan. Our results suggest that royalactin is an important lifespan-extending factor in royal jelly and acts by promoting EGF signaling in C. elegans. Further work will now be needed to clarify which (secondary) signaling pathways are activated by royalactin, and how this ultimately translates into an extended health- and lifespan.

Wang X et al. (2016) Oncotarget "Royal jelly promotes DAF-16-mediated proteostasis to tolerate -amyloid toxicity in C. elegans model of Alzheimer's disease."

Wang X, Dong Y, Cao M

[Oncotarget, 2016]

Numerous studies have demonstrated that dietary intervention may promote health and help prevent Alzheimer's disease (AD). We recently reported that bee products of royal jelly (RJ) and enzyme-treated royal jelly (eRJ) were potent to promote healthy aging in C. elegans. Here, we examined whether RJ/eRJ consumption may benefit to mitigate the AD symptom in the disease model of C. elegans. Our results showed that RJ/eRJ supplementation significantly delayed the body paralysis in AD worms, suggesting the -amyloid (A) toxicity attenuation effects of RJ/eRJ. Genetic analyses suggested that RJ/eRJ-mediated alleviation of A toxicity in AD worms required DAF-16, rather than HSF-1 and SKN-1, in an insulin/IGF signaling dependent manner. Moreover, RJ/eRJ modulated the transactivity of DAF-16 and dramatically improved the protein solubility in aged worms. Given protein solubility is a hallmark of healthy proteostasis, our findings demonstrated that RJ/eRJ supplementation improved proteostasis, and this promotion depended on the transactivity of DAF-16. Collectively, the present study not only elucidated the possible anti-AD mechanism of RJ/eRJ, but also provided evidence from a practical point of view to shed light on the extensive correlation of proteostasis and the prevention of neurodegenerative disorders.

Godfray HCJ et al. (1991) Nature "More fecund but not so fit."

Harvey PH, Godfray HCJ

[Nature, 1991]

Populations of the soil nematode Caenorhabditis elegans normally consist almost exclusively of self-fertilizing hermaphrodites. The animal first matures about 300 sperm and then a much larger number of oocytes (eggs). Nearly every sperm is used to fertilize an egg and so the maximum fecundity is around 300. Why doesn't the nematode mature more sperm and thus increase its fecundity? In a paper in the Proceedings of the Royal Society (B246, 19-24; 1991), J. Hodgkin and T.M. Barnes provide both an elegant answer and a rare insight into the mechanistic basis of an important life-history trade-off.