Phelps Grace B, Morin Jonas, Pinto Carla, Schoenfeldt Lucas, Guilmot Sebastien, Ocampo Alejandro, Perez Kevin
EPITERNA, Epalinges, Switzerland.
Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Aging Cell. 2025 Apr;24(4):e14424. doi: 10.1111/acel.14424. Epub 2025 Jan 24.
The nematode C. elegans has long served as a gold-standard model organism in aging research, particularly since the discovery of long-lived mutants in conserved aging pathways including daf-2 (IGF1) and age-1 (PI3K). Its short lifespan and small size make it highly suitable for high-throughput experiments. While numerous molecules have been tested for their effects on C. elegans lifespan, consensus is still lacking regarding the most effective and reproducible compounds. Confounding effects, especially those related to drug-bacteria interactions, remain a contentious issue in the literature. In this study, we evaluated 16 of the most frequently reported lifespan-extending molecules in C. elegans, examining their effects on lifespan with two different diets (live and UV-killed OP50). In addition, we assessed the compounds' impact on bacterial growth, their effects on various nematode strains, and the impact of the starting age of treatment. Our findings first confirmed robust lifespan extension by many, but not all, of the 16 tested compounds from the literature, and revealed that some of them could be combined to obtain additive effects. Additionally, we showed that some of these compounds also extend lifespan in the fly D. melanogaster, demonstrating a conserved effect across species. Finally, by expanding our screen to a broader pool of molecules, we identified novel lifespan-extending compounds in C. elegans.
线虫秀丽隐杆线虫长期以来一直是衰老研究中的金标准模式生物，特别是自发现包括daf - 2（IGF1）和age - 1（PI3K）在内的保守衰老途径中的长寿突变体以来。它的短寿命和小体型使其非常适合高通量实验。虽然已经测试了许多分子对秀丽隐杆线虫寿命的影响，但对于最有效和可重复的化合物仍缺乏共识。混杂效应，尤其是那些与药物 - 细菌相互作用相关的效应，在文献中仍然是一个有争议的问题。在这项研究中，我们评估了16种在秀丽隐杆线虫中最常报道的寿命延长分子，用两种不同的食物（活的和紫外线杀死的OP50）研究它们对寿命的影响。此外，我们评估了这些化合物对细菌生长的影响、它们对各种线虫菌株的作用以及治疗起始年龄的影响。我们的研究结果首先证实了文献中测试的16种化合物中的许多（但不是全部）确实能显著延长寿命，并表明其中一些化合物可以组合以获得累加效应。此外，我们表明其中一些化合物也能延长果蝇黑腹果蝇的寿命，证明了跨物种的保守效应。最后，通过将我们的筛选扩展到更广泛的分子库，我们在秀丽隐杆线虫中鉴定出了新的寿命延长化合物。
