Lifespan-Extending Effects of Royal Jelly and Its Related Substances on the Nematode Caenorhabditis elegans

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.

Royal Jelly Prevents the Progression of Sarcopenia in Aged Mice In Vivo and In Vitro

“…Because we did not assess life spans in this study, the effect of increased levels of IGF-1 by RJ/pRJ treatment on life span was not clear. However, previous studies reported that RJ/pRJ extended the life span in mice and Caenorhabditis elegans (10,11). Further studies are required to evaluate the effects and mechanisms of RJ/pRJ on life span.…”

“…Accumulating evidence suggests that RJ is rich in a wide variety of nutrients, including vitamins, minerals, and more than 20 amino acids (9). RJ also has numerous potential pharmacological capacities, such as prolonging the life span (in mice and nematodes) (10,11) and reducing fatigue (12), hypertension (13), and hypercholesterolemia, as well as antioxidant and anti-inflammatory effects (8,(14)(15)(16).…”

Determination of royal jelly freshness by ELISA with a highly specific anti-apalbumin 1, major royal jelly protein 1 antibody

“…Previous studies have demonstrated a wide range of health benefits to humans and model organisms, including vasodilative and hypotensive activities (Tokunaga et al, 2004), antitumor (Tamura et al, 1987), anti-inflammatory (Fujii et al, 1990;Kohno et al, 2004), antibacterial and disinfectant properties (Fujiwara et al, 1990;Shen et al, 2010a), antifatigue activity (Kamakura et al, 2001a), and increasing the average lifespan in mice (Inoue et al, 2003) and nematodes (Honda et al, 2011). Because of its great potential benefits to human health, RJ is widely used as a key component in many commercial products including medicine, dietary supplements, and cosmetics (Kamakura et al, 2001c).…”

Royalactin extends lifespan of Caenorhabditis elegans through epidermal growth factor signaling

“…RJ has previously been shown to extend lifespan in mice (Inoue, 2003) and in the nematode Caenorhabditis elegans (Honda et al, 2011). However, the primary factor responsible for this lifespan extension remained elusive.…”