Nutrition intervention has emerged as a potential strategy to delay aging and promote healthy longevity. Citri Reticulatae Semen (CRS) has diverse beneficial effects and has been used for thousands of years to treat pain. However, the health benefits of CRS in prolonging healthspan and improving aging-related diseases and the exact mechanisms remain poorly characterized. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to study the anti-aging and healthspan promoting activities of 75% ethanol extract of CRS (CRSE). The results showed that treatment with CRSE at 1000 μg/mL significantly extended the lifespan of worms by 18.93% without detriment to healthspan and fitness, as evidenced by the delayed aging-related phenotypes and increased body length and width and reproductive output. In addition, CRSE treatment enhanced the ability of resistance under heat, oxidative, and pathogenic bacterial stress. Consistently, heat shock proteins and antioxidant enzyme-related and pathogenesis-related (PR) genes were up-regulated by CRSE treatment. Furthermore, CRSE supplementation also improved α-synuclein, 6-OHDA, and polyQ40-induced pathologies in transgenic C. elegans models of Parkinson's disease (PD) and Huntington's disease (HD). The mechanistic study demonstrated that CRSE induced autophagy in worms, while the RNAi knockdown of 4 key autophagy-related genes including lgg-1, bec-1, vps-34, and unc-51 remarkably abrogated the beneficial effects of CRSE on the extending of lifespan and healthspan and neuroprotection, demonstrating that CRSE exerts beneficial effects via autophagy induction in worms. Together, our current findings provide new insights into the practical application of CRS for the prevention of aging and aging-related diseases.

中文翻译：

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Citri Reticulatae Semen 提取物通过秀丽隐杆线虫的自噬诱导促进健康衰老和神经保护

营养干预已成为延缓衰老和促进健康长寿的潜在策略。Citri Reticulatae Semen (CRS) 具有多种有益效果，数千年来一直被用于治疗疼痛。然而，CRS 在延长健康寿命和改善与衰老相关的疾病方面的健康益处以及确切的机制仍不清楚。在这项研究中，秀丽隐杆线虫 (C. elegans) 被用作模型生物，以研究 75% CRS 乙醇提取物 (CRSE) 的抗衰老和促进健康寿命的活性。结果表明，用 1000 μg/mL 的 CRSE 处理可显着延长线虫的寿命 18.93%，而不会损害健康寿命和健康状况，延缓衰老相关的表型以及增加的体长和宽度以及繁殖输出就是证明。此外，CRSE 处理增强了在热、氧化和致病菌胁迫下的抵抗能力。一致地，热休克蛋白和抗氧化酶相关和发病机制相关 (PR) 基因被 CRSE 处理上调。此外，补充 CRSE 还改善了帕金森氏病 (PD) 和亨廷顿氏病 (HD) 的转基因秀丽隐杆线虫模型中 α-突触核蛋白、6-OHDA 和 polyQ40 诱导的病理。机理研究表明，CRSE 可诱导线虫自噬，而 RNAi 敲低 lgg-1、bec-1、vps-34 和 unc-51 等 4 个关键自噬相关基因可显着消除 CRSE 对延长自噬的有益作用。寿命和健康跨度以及神经保护，证明 CRSE 通过蠕虫中的自噬诱导发挥有益作用。一起，