Various bioactive food compounds may confer health and longevity benefits, possibly through altering or preserving the epigenome. While bioactive food compounds are widely being marketed for human consumption as ‘improving health and longevity’ by counteracting harmful effects of poor nutrition and lifestyle, claimed effects are often not adequately documented. Using the honey bee (Apis mellifera) as a model species, we here employed a multi-step screening approach to investigate seven compounds for effects on lifespan and DNA methylation using ELISA and whole genome bisulfite sequencing (WGBS). A positive longevity effect was detected for valproic acid, isovaleric acid, and cyanocobalamin. For curcumin, we found that lifespan shortening caused by ethanol intake, was restored when curcumin and ethanol were co-administered. Furthermore, we identified region specific DNA methylation changes as a result of ethanol intake. Ethanol specific changes in DNA methylation were fully or partially blocked in honey bees receiving ethanol and curcumin together. Ethanol-affected and curcumin-blocked differentially methylated regions covered genes involved in fertility, temperature regulation and tubulin transport. Our results demonstrate fundamental negative effects of low dose ethanol consumption on lifespan and associated DNA methylation changes and present a proof-of-principle on how longevity and DNA methylation changes can be negated by the bioactive food component curcumin. Our findings provide a fundament for further studies of curcumin in invertebrates.

各种生物活性食品化合物可能通过改变或保存表观基因组而带来健康和长寿益处。虽然生物活性食品化合物被广泛销售给人类食用，通过抵消不良营养和生活方式的有害影响来“改善健康和长寿”，但其声称的效果往往没有得到充分记录。我们以蜜蜂 ( Apis mellifera ) 作为模型物种，采用多步筛选方法，利用 ELISA 和全基因组亚硫酸氢盐测序 (WGBS) 来研究七种化合物对寿命和 DNA 甲基化的影响。检测到丙戊酸、异戊酸和氰钴胺具有积极的长寿作用。对于姜黄素，我们发现当姜黄素和乙醇共同服用时，由乙醇摄入引起的寿命缩短可以得到恢复。此外，我们还发现了乙醇摄入导致的区域特异性 DNA 甲基化变化。在同时接受乙醇和姜黄素的蜜蜂中，DNA甲基化的乙醇特异性变化被完全或部分阻断。乙醇影响和姜黄素阻断的差异甲基化区域覆盖了与生育力、温度调节和微管蛋白运输有关的基因。我们的结果证明了低剂量乙醇消耗对寿命和相关 DNA 甲基化变化的根本负面影响，并提供了关于生物活性食品成分姜黄素如何消除寿命和 DNA 甲基化变化的原理验证。我们的研究结果为进一步研究无脊椎动物中的姜黄素奠定了基础。