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

Abstract

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.

Baicalein modulates stress-resistance and life span in C. elegans via SKN-1 but not DAF-16

“…elegans is a well-established model in genetics 9 but is currently also used to analyze biological effects of natural compounds in a complete, simple structured organism [10][11][12] . C. elegans possesses a homology to 60-80% of the human genome 13 , especially a high number of signaling pathways are conserved in this organism 14 .…”

Royal jelly promotes DAF-16-mediated proteostasis to tolerate β-amyloid toxicity inC. elegansmodel of Alzheimer's disease

“…As we previously reported that 2mg/ml RJ and 1mg/ml eRJ significantly prolonged C. elegans lifespan, the same concentrations of RJ and eRJ were adopted in this study [18]. In brief, synchronous CL2006 L4/young adult worms were treated with or without RJ/eRJ (2mg/mL and 1mg/mL, respectively) at 20°C and paralyses were measured every day until all AD worms were paralyzed.…”

“…Our previous studies showed that IIS and DAF-16 played an essential role in RJ/eRJ-mediated lifespan extension and stress resistance [18]. Considering the potential link between prolongevity and anti-AD function, we wondered whether IIS and DAF-16 also played an imperative role in RJ/eRJ-mediated protection against Aβ toxicity.…”

“…Numerous studies have shown that active ingredients from functional foods potently promote healthy aging [14–18], implying that dietary intervention may be a feasible means to prevent or delay the onset of AD. Royal jelly (RJ) and enzyme-treated RJ (eRJ) are consumed as functional foods due to their beneficial effects, such as antimicrobial, anti-inflammation, immune-modulation, and anti-oxidation [19, 20].…”

“…eRJ is produced by digestion of RJ with a hydrolytic enzyme to decrease the allergenic properties [22]. We recently reported that supplementation of both RJ and eRJ significantly promoted lifespan and stress resistance in C. elegans [18]. Given that certain nutraceuticals with prolongevity effects may promote proteostasis and attenuate proteotoxicity [17], it is intriguing to test whether RJ/eRJ is able to influence the proteostasis network to prevent or delay AD.…”