Autophagy is a conserved intracellular catabolic pathway that removes cytoplasmic components to contribute to neuronal homeostasis. Accumulating evidence has increasingly shown that the induction of autophagy improves neuronal health and extends longevity in several animal models. Therefore, there is a great interest in the identification of effective autophagy enhancers with potential nutraceutical or pharmaceutical properties to ameliorate age-related diseases, such as neurodegenerative disorders, and/or promote longevity. Queen bee acid (QBA, 10-hydroxy-2-decenoic acid) is the major fatty acid component of, and is found exclusively in, royal jelly, which has beneficial properties for human health. It is reported that QBA has antitumor, anti-inflammatory, and antibacterial activities and promotes neurogenesis and neuronal health; however, the mechanism by which QBA exerts these effects has not been fully elucidated. The present study investigated the role of the autophagic process in the protective effect of QBA. We found that QBA is a novel autophagy inducer that triggers autophagy in various neuronal cell lines and mouse and fly models. The beclin-1 (BECN1) and mTOR pathways participate in the regulation of QBA-induced autophagy. Moreover, our results showed that QBA stimulates sirtuin 1 (SIRT1), which promotes autophagy by the deacetylation of critical ATG proteins. Finally, QBA-mediated autophagy promotes neuroprotection in Parkinson’s disease in vitro and in a mouse model and extends the lifespan of Drosophila melanogaster. This study provides detailed evidences showing that autophagy induction plays a critical role in the beneficial health effects of QBA.

自噬是一种保守的细胞内分解代谢途径，可去除细胞质成分以促进神经元稳态。越来越多的证据表明，在几种动物模型中，自噬的诱导可以改善神经元健康并延长寿命。因此，人们对鉴定具有潜在营养或药物特性的有效自噬增强剂非常感兴趣，以改善与年龄相关的疾病，例如神经退行性疾病，和/或促进长寿。蜂王酸（QBA，10-羟基-2-癸烯酸）是蜂王浆的主要脂肪酸成分，并且仅存在于蜂王浆中，对人类健康具有有益的特性。据报道，QBA具有抗肿瘤、抗炎、抗菌活性，促进神经发生和神经元健康；然而，QBA 发挥这些作用的机制尚未完全阐明。本研究调查了自噬过程在 QBA 保护作用中的作用。我们发现 QBA 是一种新型自噬诱导剂，可在各种神经元细胞系以及小鼠和苍蝇模型中触发自噬。beclin-1 (BECN1) 和 mTOR 通路参与 QBA 诱导的自噬的调节。此外，我们的结果表明，QBA 会刺激 Sirtuin 1 (SIRT1)，后者通过关键 ATG 蛋白的脱乙酰化来促进自噬。最后，QBA 介导的自噬可在体外和小鼠模型中促进帕金森病的神经保护，并延长果蝇的寿命。这项研究提供了详细的证据，表明自噬诱导在 QBA 的有益健康影响中发挥着关键作用。