Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, 4202 E. Fowler Ave, ISA 2015, Tampa, FL, 33620, USA.
Cell Stress Chaperones. 2018 Jan;23(1):65-75. doi: 10.1007/s12192-017-0824-7. Epub 2017 Jul 4.
As the population ages, there is a critical need to uncover strategies to combat diseases of aging. Studies in the soil-dwelling nematode Caenorhabditis elegans have demonstrated the protective effects of coffee extract and caffeine in promoting the induction of conserved longevity pathways including the insulin-like signaling pathway and the oxidative stress response. We were interested in determining the effects of coffee and caffeine treatment on the regulation of the heat shock response. The heat shock response is a highly conserved cellular response that functions as a cytoprotective mechanism during stress, mediated by the heat shock transcription factor HSF-1. In the worm, HSF-1 not only promotes protection against stress but is also essential for development and longevity. Induction of the heat shock response has been suggested to be beneficial for diseases of protein conformation by preventing protein misfolding and aggregation, and as such has been proposed as a therapeutic target for age-associated neurodegenerative disorders. In this study, we demonstrate that coffee is a potent, dose-dependent, inducer of the heat shock response. Treatment with a moderate dose of pure caffeine was also able to induce the heat shock response, indicating caffeine as an important component within coffee for producing this response. The effects that we observe with both coffee and pure caffeine on the heat shock response are both dependent on HSF-1. In a C. elegans Huntington's disease model, worms treated with caffeine were protected from polyglutamine aggregates and toxicity, an effect that was also HSF-1-dependent. In conclusion, these results demonstrate caffeinated coffee, and pure caffeine, as protective substances that promote proteostasis through induction of the heat shock response.
随着人口老龄化，迫切需要发现对抗衰老相关疾病的策略。对土壤线虫秀丽隐杆线虫的研究表明，咖啡提取物和咖啡因具有保护作用，可以促进包括胰岛素样信号通路和氧化应激反应在内的保守长寿途径的诱导。我们有兴趣确定咖啡和咖啡因处理对热休克反应调控的影响。热休克反应是一种高度保守的细胞反应，作为应激时的细胞保护机制，由热休克转录因子 HSF-1 介导。在蠕虫中，HSF-1 不仅促进对压力的保护，而且对发育和长寿也是必不可少的。热休克反应的诱导被认为通过防止蛋白质错误折叠和聚集对蛋白质构象疾病有益，因此被提议作为与年龄相关的神经退行性疾病的治疗靶点。在这项研究中，我们证明咖啡是一种强有力的、剂量依赖性的热休克反应诱导剂。纯咖啡因的中等剂量处理也能诱导热休克反应，表明咖啡因是咖啡中产生这种反应的重要成分。我们观察到咖啡和纯咖啡因对热休克反应的影响都依赖于 HSF-1。在秀丽隐杆线虫亨廷顿病模型中，用咖啡因处理的蠕虫可以防止多聚谷氨酰胺聚集和毒性，这种作用也依赖于 HSF-1。总之，这些结果表明含咖啡因的咖啡和纯咖啡因是通过诱导热休克反应来促进蛋白质稳态的保护物质。
