Asperuloside, the bioactive compound in the edible Eucommia ulmoides male flower, delays muscle aging by daf-16 mediated improvement in mitochondrial dysfunction.

Muscle aging is accompanied by a progressive decline in motor performance and mitochondrial function, yet fundamental treatments for this disorder remain sparse. The search for active compounds from natural dietary products that promote muscular health has attracted considerable interest. Although the male flowers of Eucommia ulmoides Oliv., an emerging resource of plant-based food, have healthspan-promoting efficacy, it's still unclear whether they or their main active compounds (iridoids) could improve muscle aging. We compared the effects of three iridoids on motion status during different aging processes in Caenorhabditis elegans (C. elegans). Additionally, we further investigated the roles and mechanisms of the iridoid-rich floral extract (EUFE) and the most active monomer on nematode age-related muscle hypofunction exacerbated by high fat. We found that EUFE and asperuloside (Asp) significantly improved motility and muscular health and reduced lipid accumulation at appropriate concentrations. Compared to normal mitochondria against muscle disorder, Asp delayed the deterioration of mitochondrial function, morphology, or related metabolism during aging. Meanwhile, Asp regulated the mitochondrial quality control (MQC) network, mainly activating mitophagy, which was associated with increased mRNA and protein expression of lgg-1 and dct-1. Mechanistically, Asp promoted the expression and nuclear localization of the DAF-16 protein, an upstream regulator of the above two autophagy-related genes. The defective mutant and RNA interference further suggested that daf-16 mediated the ameliorative effects of Asp on muscle aging and mitochondrial dysfunction. These results provide potential evidence for the preventive application and functional food development of E. ulmoides male flowers and asperuloside against muscle aging.

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 C. elegans, and the Eucommia ulmoides male flower was screened out by comparing centrally. The lifespan of C. elegans increased by 18.61% under the treatment of 100 µg mL-1 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 C. elegans 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 daf-16, drp-1, eat-3, lgg-1, and dct-1 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.