Li Ai-Pei, Li Dan, Tan Xin, Xu Rui, Mao Lin-Xi, Kang Juan-Juan, Li Sheng-Hong, Liu Yan
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China.
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, China.
Food Funct. 2025 May 6;16(9):3369-3383. doi: 10.1039/d5fo01157d.
Aging represents a significant global challenge characterized by persistent oxidative stress and dysregulated lipid metabolism. Crocin, the primary bioactive constituent of saffron ( L.), is widely utilized as a natural food colorant and exhibits potent anti-inflammatory and antioxidant properties. Previous studies have demonstrated crocin's antioxidative, neuroprotective and memory-enhancing effects in aged rats; however, its direct impact on aging and the underlying mechanisms remain unexplored. In this study, we demonstrated that crocin treatment extended lifespan, enhanced survival under heat and juglone-induced oxidative stress, and reduced lipofuscin accumulation in the model organism . Mechanistically, crocin activated DAF-16, the homolog of human FOXO, resulting in the upregulation of key antioxidant genes (, and ). Notably, the lifespan-extension effect of crocin was abolished in a mutant, and its antioxidant effects were significantly attenuated in RNAi experiments conducted in N2, CL2166, CF1553 and TJ375 strains. Furthermore, crocin specifically reduced fat accumulation, and upregulated the expression of genes involved in lipid mobilization (, , and ) and unsaturated fatty acid synthesis ( and ) in aged nematodes. GC-MS analysis further demonstrated that crocin treatment elevated the levels of unsaturated fatty acids (C18:1n9, C20:4n-6, C20:4n-3 and C20:5n-3), an effect that was completely abolished under knockdown conditions. Collectively, these findings suggest that crocin promotes longevity in by mitigating oxidative stress and modulating lipid metabolism through the DAF-16/FOXO pathway. These results highlight the potential of crocin as a promising strategy for treating aging and age-related diseases.
衰老代表着一项重大的全球性挑战，其特征为持续的氧化应激和脂质代谢失调。藏红花素是藏红花（Crocus sativus L.）的主要生物活性成分，被广泛用作天然食品着色剂，并具有强大的抗炎和抗氧化特性。先前的研究已证明藏红花素对老年大鼠具有抗氧化、神经保护和增强记忆的作用；然而，其对衰老的直接影响及潜在机制仍未得到探索。在本研究中，我们证明藏红花素处理可延长寿命，增强在热应激和胡桃醌诱导的氧化应激下的存活率，并减少模式生物中的脂褐素积累。从机制上讲，藏红花素激活了人类FOXO的同源物DAF-16，导致关键抗氧化基因（sod-3、ctl-1和gcs-1）的上调。值得注意的是，在daf-16突变体中，藏红花素的寿命延长效应被消除，并且在N2、CL2166、CF1553和TJ375菌株中进行的daf-16 RNA干扰实验中，其抗氧化作用显著减弱。此外，藏红花素特异性地减少了脂肪积累，并上调了老年线虫中参与脂质动员（atgl-1、lipl-4、lipl-5和lipl-6）和不饱和脂肪酸合成（fat-5和fat-6）的基因表达。气相色谱-质谱分析进一步表明，藏红花素处理提高了不饱和脂肪酸（C18:1n9、C20:4n-6、C20:4n-3和C20:5n-3）的水平，在daf-16基因敲低条件下，这一效应完全被消除。总体而言，这些发现表明藏红花素通过减轻氧化应激并通过DAF-16/FOXO途径调节脂质代谢来促进秀丽隐杆线虫的长寿。这些结果突出了藏红花素作为治疗衰老及与年龄相关疾病的一种有前景策略的潜力。
