7 Papers found (0.012 seconds)

Tseng RJ et al. (2007) Mol Genet Genomics "The bromodomain protein LEX-1 acts with TAM-1 to modulate gene expression in C. elegans."

Armstrong KR, Tseng RJ, Chamberlin HM, Wang X

[

Mol Genet Genomics,

2007]

In many organisms, repetitive DNA serves as a trigger for gene silencing. However, some gene expression is observed from repetitive genomic regions such as heterochromatin, suggesting mechanisms exist to modulate the silencing effects. From a genetic screen in C. elegans, we have identified mutations in two genes important for expression of repetitive sequences: lex-1 and tam-1. Here we show that lex-1 encodes a protein containing an ATPase domain and a bromodomain. LEX-1 is similar to the yeast Yta7 protein, which maintains boundaries between silenced and active chromatin. tam-1 has previously been shown to encode a RING finger/B-box protein that modulates gene expression from repetitive DNA. We find that lex-1, like tam-1, acts as a class B synthetic multivulva (synMuv) gene. However, since lex-1 and tam-1 mutants have normal P granule localization, it suggests they act through a mechanism distinct from other class B synMuvs. We observe intragenic (interallelic) complementation with lex-1 and a genetic interaction between lex-1 and tam-1, data consistent with the idea that the gene products function in the same biological process, perhaps as part of a protein complex. We propose that LEX-1 and TAM-1 function together to influence chromatin structure and to promote expression from repetitive sequences.

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."

Dong Y, Cao M, Wang X, Grasso LM, 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.

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, Cao M, Dong Y

[

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.

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

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

[

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 Caenorhabditis elegans (C. elegans), a nematode model. The aim of this study was to investigate the potential benefits of RJ supplementation on modulation of the innate immunity in C. elegans. Using Staphylococcus aureus (S. aureus; ATCC 25923) as the infection model, we showed that RJ supplementation from the egg hatching stage could protect C. elegans 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 C. elegans, 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.

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

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

[

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.

Zhang G et al. (2005) Mech Dev "Alteration of the DNA binding domain disrupts distinct functions of the C. elegans Pax protein EGL-38."

Wang X, Rajakumar V, Sleiman SF, Chamberlin HM, Zhang G, Tseng RJ

[

Mech Dev,

2005]

The paired-domain-containing Pax transcription factors play an important role in the development of a range of organ, tissue and cell types. Although DNA binding elements and target genes for Pax proteins have been identified, how these proteins identify appropriate DNA elements and regulate different genes in different cellular contexts is not well understood. To investigate the relationship between Pax proteins and their targets, we have studied the in vivo and in vitro properties associated with wild-type and different mutant variants of the Caenorhabditis elegans Pax protein EGL-38. Here, we characterize the properties of four mutations that result in an amino acid substitution in the DNA binding domain of EGL-38. We find that animals bearing the different mutant alleles exhibit tissue-preferential defects in egl-38 function. The mutant proteins are also altered in their activity in an ectopic expression assay and in their in vitro DNA binding properties. Using in vitro selection, we have identified binding sites for EGL-38. However, we show that selected sites function poorly in vivo as EGL-38 response elements, indicating that sequence features in addition to DNA binding determine the efficacy of Pax response elements. The distinction between DNA binding and activity is consistent with the model that other factors commonly play a role in mediating Pax protein target site selection and function in vivo.

Honda Y et al. (2015) J Aging Res "10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling."

Araki Y, Ichihara K, Ito M, Honda Y, Tanaka M, Honda S, Hata T

[

J Aging Res,

2015]

Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.