Eucommia ulmoides male flower as a remarkable edible floral resource exerts lifespan/healthspan-promoting effects on Caenorhabditis elegans .

Natural products, especially phytochemicals, can effectively improve the health of various model organisms and ultimately prolong their lifespan. As an emerging resource of plant-based food, edible flowers have potential anti-aging effects. Here, we showed that twelve out of 30 drug-food homologous flowers' extracts significantly extended the lifespan of , and the male flower was screened out by comparing centrally. The lifespan of increased by 18.61% under the treatment of 100 μg mL floral extract (EUFE). Interestingly, this effect was attenuated when EUFE was administered late or at higher concentrations. Significantly, EUFE improved health indicators that decline with aging including pharyngeal pumping, mobility, muscle morphology, and lipofuscin accumulation. EUFE also enhanced the resistance of to oxidative/heat stress. The longevity-extending effect of EUFE was dependent on transcription factor DAF-16 and mitochondrial function. Moreover, EUFE triggered the nuclear translocation of DAF-16 and promoted downstream LGG-1 and SOD3 protein expression. In body-wall muscles, EUFE stimulated mitochondrial fission and mitophagy to mitigate age-related mitochondrial impairments. The transcriptional checkpoints of , , , , and further showed that EUFE regulated DAF-16 signaling and mitochondrial homeostasis. Finally, the interpretation of the EUFE components by correlation analysis, UHPLC-QE-MS, and verification experiments showed that aucubin, geniposide, and asperuloside are the main active compounds. We revealed the excellent lifespan/healthspan-promoting efficacy of EUFE and highlighted that edible flowers are worthy of further investigation as anti-aging dietary resources. Meanwhile, related mechanisms enriched the hypothesis that mitochondria might be involved in the healthspan modulation of longevity pathways.