Smith RJ et al. (1988) Trop Med Parasitol "Vascular perfusion of Onchocerca volvulus nodules."

Williams JF, Smith RJ, Guderian RH, Cotter TP

[Trop Med Parasitol, 1988]

Perfusion of the vascular bed was achieved in 24 freshly excised nodules of Onchocerca volvulus varying from 0.5 to 2 cm in diameter. India Ink, Microfil polymer, or acrylate perfusates were passed through the vascular supply via cannulation of superficial capsular vessels. After clearing in glycerol or methyl salicylate, or KOH corrosion in the case of the acrylate, nodules were examined microscopically. Small nodules had an extensive blood supply, diffusely distributed throughout the nodule matrix, and in close association with the coils of the worms. In bigger nodules the central area appeared more dense, and intense vascularization appeared to be more peripheral; in the largest nodules the central core was not well vascularized, but a band of heavy vascularization was seen at the margin of the core, fed by superficial vessels and in close contact with worm coils. Very fine branches of the vascular tree were perfused by all three contrast media, but histologically there was evidence of incomplete filling of the smallest vessels. However, there was no extravasation of per-fusates around parasites, even where the approximation between between vessels and parasite surfaces was close. The possibility is considered that O. volvulus may control blood vessel proliferation by release of angiogenesis factors, analogous to rapidly growing solid tumors.

Hampton-Smith RJ et al. (2009) Ann N Y Acad Sci "From polyps to people: a highly familiar response to hypoxia."

Hampton-Smith RJ, Peet DJ

[Ann N Y Acad Sci, 2009]

Obligate aerobes, by definition, require oxygen in order to sustain life. Therefore, changes in environment or physiology that cause metabolic demand for oxygen to exceed supply (hypoxia) can be highly detrimental. Despite considerable variation in physiology and habitat between species, a majority of metazoa employ homologues of the hypoxia-inducible factor (HIF) transcription factors to adapt to oxygen deprivation. Studies in mammals, Drosophila and C. elegans have shown that regulation of HIF-alpha by prolyl hydroxylase (PHD)-mediated proteasomal degradation is conserved, as are a number of HIF target genes. More recently, analysis of coral and beetle HIFs has revealed that, unlike flies and worms, the C-terminal transactivation domain of HIF-alpha and its regulatory hydroxylase FIH-1 are also preserved. The reasons for variable conservation of this system are unknown. However, discovery of the "intermediary" properties of the beetle HIF pathway may prove a useful tool to better define HIF signaling in both mammals and invertebrates.

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.

Wang X et al. (2015) J Gerontol A Biol Sci Med Sci "Royal Jelly-Mediated Prolongevity and Stress Resistance in Caenorhabditis elegans Is Possibly Modulated by the Interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 Proteins."

Grasso LM, Wang X, Cao M, Dong Y, Cook LF

[J Gerontol A Biol Sci Med Sci, 2015]

Recent studies suggest that royal jelly (RJ) and its related substances may have antiaging properties. However, the molecular mechanisms underlying the beneficial effects remain elusive. We report that the effects of RJ and enzyme-treated RJ (eRJ) on life span and health span in Caenorhabditis elegans (C elegans) are modulated by the sophisticated interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 proteins. Dietary supplementation with RJ or eRJ increased C. elegans life span in a dose-dependent manner. The RJ and eRJ consumption increased the tolerance of C elegans to oxidative stress, ultraviolet irradiation, and heat shock stress. Our genetic analyses showed that RJ/eRJ-mediated life-span extension requires insulin/IGF-1 signaling and the activities of DAF-16, SIR-2.1, HCF-1, and FTT-2, a 14-3-3 protein. Earlier studies reported that DAF-16/FOXO, SIR-2.1/SIRT1, FTT-2, and HCF-1 have extensive interplays in worms and mammals. Our present findings suggest that RJ/eRJ-mediated promotion of longevity and stress resistance in C elegans is dependent on these conserved interplays. From an evolutionary point of view, this study not only provides new insights into the molecular mechanisms of RJ's action on health span promotion in C elegans, but also has imperative implications in using RJ/eRJ as nutraceuticals to delay aging and age-related disorders.

Natarajan O et al. (2020) J Med Food "The Immunomodulatory Effects of Royal Jelly on Defending Against Bacterial Infections in the Caenorhabditis elegans Model."

Angeloni JT, Dong Y, Bilodeau MF, Russi KE, Cao M, Natarajan O

[J Med Food, 2020]

Emerging evidence suggests that aging is associated with the deterioration of immunity, a term known as immunosenescence, which may lead to a higher incidence of infections in the elderly population. Our previous studies reported that supplementation of royal jelly (RJ) extended the lifespan of <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), a nematode model. The aim of this study was to investigate the potential benefits of RJ supplementation on modulation of the innate immunity in <i>C. elegans</i>. Using <i>Staphylococcus aureus</i> (<i>S. aureus</i>; ATCC 25923) as the infection model, we showed that RJ supplementation from the egg hatching stage could protect <i>C. elegans</i> against the infection. Further mechanistic studies demonstrated that RJ coordinated pathways of IIS/DAF-16, p38 MAPK, and Wnt to modulate the innate immunity. In addition, when RJ was administrated to the aged <i>C. elegans</i>, the worms displayed prolonged survival time to a variety of bacterial infections compared with the nontreatment group. This result indicates the RJ may help delay the innate immunosenescence.

Kunugi H et al. (2019) Int J Mol Sci "Royal Jelly and Its Components Promote Healthy Aging and Longevity: From Animal Models to Humans."

Kunugi H, Mohammed Ali A

[Int J Mol Sci, 2019]

Aging is a natural phenomenon that occurs in all living organisms. In humans, aging is associated with lowered overall functioning and increased mortality out of the risk for various age-related diseases. Hence, researchers are pushed to find effective natural interventions that can promote healthy aging and extend lifespan. Royal jelly (RJ) is a natural product that is fed to bee queens throughout their entire life. Thanks to RJ, bee queens enjoy an excellent reproductive function and lengthened lifespan compared with bee workers, despite the fact that they have the same genome. This review aimed to investigate the effect of RJ and/or its components on lifespan/healthspan in various species by evaluating the most relevant studies. Moreover, we briefly discussed the positive effects of RJ on health maintenance and age-related disorders in humans. Whenever possible, we explored the metabolic, molecular, and cellular mechanisms through which RJ can modulate age-related mechanisms to extend lifespan. RJ and its ingredients-proteins and their derivatives e.g., royalactin; lipids e.g., 10-hydroxydecenoic acid; and vitamins e.g., pantothenic acid-improved healthspan and extended lifespan in worker honeybees <i>Apis mellifera</i>, <i>Drosophila Melanogaster</i> flies, <i>Gryllus bimaculatus</i> crickets, silkworms, <i>Caenorhabditis elegans</i> nematodes, and mice. The longevity effect was attained via various mechanisms: downregulation of insulin-like growth factors and targeting of rapamycin, upregulation of the epidermal growth factor signaling, dietary restriction, and enhancement of antioxidative capacity. RJ and its protein and lipid ingredients have the potential to extend lifespan in various creatures and prevent senescence of human tissues in cell cultures. These findings pave the way to inventing specific RJ anti-aging drugs. However, much work is needed to understand the effect of RJ interactions with microbiome, diet, activity level, gender, and other genetic variation factors that affect healthspan and longevity.

Honda Y et al. (2011) PLoS One "Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans."

Araki Y, Maruyama H, Ito M, Ichihara K, Kojima T, Tanaka M, Honda S, Fujita Y, Sato A, Nozawa Y, Honda Y

[PLoS One, 2011]

BACKGROUND: One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action. PRINCIPAL FINDINGS: We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical interventions in the aging process.

Rosenberg R (1978) Worm Breeder's Gazette

Rosenberg R

[Worm Breeder's Gazette, 1978]

All eyes are on the newest fashion trend, the Dumpy Look . Pace setting designer I.M. Worm s androgynous wardrobe is all the rage in Paris. Bianca Jagger quips, Tres, tres - Women s Wear Daily writes, Elegans personified - Patti Smith thinks, The punks won t buy it and Craig Russell says, It fits right in with my act . A product of Mutant Isolation, Inc.

Kravtsov, V. et al. (2013) International Worm Meeting "The effects of aging on dendritic plasticity and PVD-FLP branch coexistence."

Podbilewicz, B., Oren-Suissa, M., Kravtsov, V.

[International Worm Meeting, 2013]

Self-avoidance, tiling and coexistence are the main mechanisms that enable the best dendritic coverage. C. elegans undergoes aging-associated changes that ultimately lead to decreased functionality of the organism, including its neurological functions. Recent research has shown that the nervous system of C. elegans undergoes changes and alterations during aging including dendritic morphology (Tank et al., 2011). We study dendritic plasticity, aging and spatial dendritic organization of two highly arborized mechanoreceptors in C. elegans, PVD and FLP (Oren-Suissa et al., 2010). PVD dendrites of L4s and young adults show regenerative ability following dendrotomy (laser induced severing of dendrites). Our working hypothesis is that in older ages this ability to regenerate is compromised. Previous studies and our preliminary results indicate that PVD and FLP do not overlap in larval stages (Smith et al., 2010). In addition, dendrites within each bilateral PVD do not overlap through a self-avoidance mechanism (Smith et al., 2012). We found that (1) the coverage fields of the PVD and FLP overlap in adult worms, which indicates coexistence and not tiling. This overlap increases as the worm ages. (2) PVDs show aberrant arborization at the age of 9 days of adulthood. (3) Dramatic increase in self-avoidance defects as animals age. In humans many neurodegenerative diseases as well as generalized cognitive decline are associated with age, aberrant arborization or both (e.g. autism and Alzheimer's disease). However our understanding of how these disorders are triggered and aggravated is scarce. Our research provides an insight into the aging and regeneration process of individual neurons. Oren-Suissa, M., et al. (2010). Science 328, 1285-1288. Smith, C.J. et al. (2010). Developmental Biology 345, 18-33. Smith, C.J., et al. (2012). Nature Neuroscience 15, 731-737. Tank, E.M.H. et al. (2011). Journal of Neuroscience 31, 9279-9288.

Cassada RC et al. (1980) Worm Breeder's Gazette "initial characterization of ts embryonic defective (emb) mutants (Goettingen set)."

Culotti MR, Cassada RC, Von Ehrenstein G, Isnenghi E

[Worm Breeder's Gazette, 1980]

[See Figure 1] Already published allelism: Wood et al., 1980: b117=b189; b246 = let- 2.Miwa et al., 1980: hc57 = hc62; hc61 = hc67. Our global complementation results: g1 = g4; g16 = g65 = hc61 = hc67; g36 = hc65; g23 = g34 = hc70 = b117 = b189; g37 = b246 = let-2; b84 = hc66; g14 = g43; g57 = b1O. From frequency of multiple alleles we estimate 200-400 genes essential for embryogenesis. Mapping is in progress. We are also doing tsp's, R + H Tests, and cellular defects ( Isnenghi, Cassada, Radnia, Schierenberg, K. Smith, v. Ehrenstein).