AlOkda Abdelrahman, Yadav Shweta, Pacis Alain, Parkhitko Andrey A, Van Raamsdonk Jeremy M
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Metabolic Disorders and Complications Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
bioRxiv. 2025 Aug 1:2025.08.01.668202. doi: 10.1101/2025.08.01.668202.
As aging is the primary risk factor for many chronic diseases, geroscience aims to target aging to delay age-related decline. Here, we identify Cyrene (dihydrolevoglucosenone), a sustainable, biocompatible solvent, as a novel geroprotective compound. Cyrene extends lifespan and healthspan in , improving locomotor function and resistance to oxidative, thermal, osmotic, genotoxic, and proteotoxic stress. It also confers protection in neurodegenerative models of Alzheimer's, Parkinson's, and Huntington's disease. Cyrene is effective when delivered during development or early adulthood and requires administration before day 8 to extend longevity. Its benefits are independent of bacterial metabolism and partially independent of the FOXO transcription factor DAF-16. Importantly, Cyrene also extends lifespan and enhances oxidative stress resistance in , demonstrating cross-species efficacy. These findings identify Cyrene as a novel geroprotective compound that promotes longevity, resilience, and neuroprotection. Conservation across species supports future work to dissect molecular mechanisms and test its potential in mammals.
由于衰老为许多慢性疾病的主要风险因素，老年科学旨在针对衰老来延缓与年龄相关的衰退。在此，我们确定了一种可持续的生物相容性溶剂——环戊酮（二氢左旋葡萄糖酮），它是一种新型的老年保护化合物。环戊酮可延长秀丽隐杆线虫的寿命和健康寿命，改善其运动功能，并增强其对氧化、热、渗透、基因毒性和蛋白毒性应激的抵抗力。它还能在阿尔茨海默病、帕金森病和亨廷顿病的神经退行性模型中提供保护。环戊酮在发育期间或成年早期给药时有效，且需要在第8天之前给药以延长寿命。其益处独立于细菌代谢，且部分独立于FOXO转录因子DAF-16。重要的是，环戊酮还能延长果蝇的寿命并增强其抗氧化应激能力，证明了其跨物种功效。这些发现确定环戊酮是一种新型的老年保护化合物，可促进长寿、恢复力和神经保护。跨物种的保守性为未来剖析分子机制并测试其在哺乳动物中的潜力的工作提供了支持。
