Park Suhyeon, Kim Bo-Kyoung, Park Sang-Kyu
Department of Medical Sciences, General Graduate School, Soonchunhyang University, Asan 31538, Chungnam, Republic of Korea.
Department of Medical Biotechnology, Soonchunhyang University, Asan 31538, Chungnam, Republic of Korea.
Pharmaceuticals (Basel). 2022 Dec 8;15(12):1528. doi: 10.3390/ph15121528.
Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonoid abundant in various fruits and vegetables, including apple, strawberry, and onion, shows several beneficial effects such as anti-oxidant, anti-inflammatory, and anti-tumor effects. The free radical theory of aging suggests that age-related accumulation of oxidative damage is the major cause of aging and that decreasing cellular oxidative stress can regulate aging. Here, we investigated the effects of dietary supplementation with fisetin on the stress response, aging, and age-related diseases. Fisetin reduced the cellular ROS levels and increased the resistance to oxidative stress. However, the response to UV irradiation was not affected by fisetin. Both the mean and maximum lifespans were significantly extended by fisetin; lifespan extension by fisetin was accompanied by reduced fertility as a trade-off. Age-related decline in motility was also delayed by supplementation with fisetin. Amyloid beta-induced toxicity was markedly decreased by fisetin, which required DAF-16 and SKN-1. Reduced motility induced by a high-glucose diet was completely recovered by supplementation with fisetin, which was dependent on SKN-1. Using a Parkinson's disease model, we showed that degeneration of dopaminergic neurons was significantly inhibited by treatment with fisetin. Genetic analysis revealed that lifespan extension by fisetin was mediated by DAF-16-induced stress response and autophagy. These findings support the free radical theory of aging and suggest that fisetin can be a strong candidate for use in novel anti-aging anti-oxidant nutraceuticals.
漆黄素（3,3',4',7-四羟基黄酮）是一种在各种水果和蔬菜中含量丰富的黄酮类化合物，包括苹果、草莓和洋葱，具有多种有益作用，如抗氧化、抗炎和抗肿瘤作用。衰老的自由基理论表明，与年龄相关的氧化损伤积累是衰老的主要原因，降低细胞氧化应激可以调节衰老。在此，我们研究了饮食中补充漆黄素对应激反应、衰老和与年龄相关疾病的影响。漆黄素降低了细胞内活性氧水平，增强了对氧化应激的抵抗力。然而，漆黄素对紫外线照射的反应没有影响。漆黄素显著延长了平均寿命和最大寿命；作为一种权衡，漆黄素延长寿命伴随着生育能力的降低。补充漆黄素也延缓了与年龄相关的运动能力下降。漆黄素显著降低了β-淀粉样蛋白诱导的毒性，这需要DAF-16和SKN-1。补充漆黄素完全恢复了高糖饮食诱导的运动能力下降，这依赖于SKN-1。使用帕金森病模型，我们表明漆黄素治疗显著抑制了多巴胺能神经元的退化。基因分析表明，漆黄素延长寿命是由DAF-16诱导的应激反应和自噬介导的。这些发现支持衰老的自由基理论，并表明漆黄素可能成为新型抗衰老抗氧化营养保健品的有力候选物。
