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

Abstract

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.