Abstract
BackgroundOne 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 FindingsWe 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/SignificanceThese 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.
Highlights
Lifespan in metazoans is influenced by genetic factors [1], [2] and by environmental factors, including temperature [3], [4], oxygen [5,6,7], food intake [8] and nutrition [9,10,11,12,13,14,15,16]
Royal jelly (RJ) treatment at 10 mg/ml extended the mean lifespan by 7–9%, whereas either 1 or 100 mg/ml RJ had little or no effects on the lifespan (Fig. 1, Table S1), indicating that there is an optimal dose of RJ for lifespan extension
These results suggest that both RJ and protease-treated RJ (pRJ) contain the lifespanextending agents and that these agents are not proteinaceus
Summary
Lifespan in metazoans is influenced by genetic factors [1], [2] and by environmental factors, including temperature [3], [4], oxygen [5,6,7], food intake [8] and nutrition [9,10,11,12,13,14,15,16]. Workers are fed this RJ for only a short period of time during their larval stages. This scenario raises the possibility that RJ contains longevity-promoting agents for queens [17], [19]. The mechanism by which RJ exerts its longevity effects on queen bees and the identities of the components that play critical roles in this process are largely unknown. 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
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