Phytochemical-rich <i>Eucommia ulmoides</i> leaf extract extends healthspan in <i>Caenorhabditis elegans</i> via the <i>pmk-1</i>/p38 MAPK pathway and mitochondrial homeostasis.

<h4>Objectives</h4>As a medicinal and edible resource, <i>Eucommia ulmoides</i> leaf (EUL) shows considerable promise in facilitating healthy aging. However, its precise biological mechanisms remain unclear. This study aimed to investigate the anti-aging efficacy and underlying pathways of <i>Eucommia ulmoides</i> leaf extract (EULE) using the <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) model.<h4>Methods</h4>Phytochemical profiling of the extract was performed. <i>C. elegans</i> were supplemented with the extract, and the effects on lifespan, healthspan(definition) indicators (muscle deterioration, intestinal barrier function, mitochondrial homeostasis), and gene expression were evaluated via transcriptomic analysis.<h4>Results</h4>Phytochemical analysis revealed that the extract is abundant in bioactive compounds such as flavonoids, iridoids, and lignans. Supplementation with the extract significantly prolonged the lifespan of <i>C. elegans</i> by up to 14.69% and improved healthspan by alleviating age-related muscle deterioration, preserving intestinal barrier function, and regulating mitochondrial homeostasis. Transcriptomic analysis identified the mitogen activated protein kinase (MAPK) signaling pathway as the primary mediator of these anti-aging benefits.<h4>Conclusions</h4>These results provide robust evidence supporting the use of EUL as a natural dietary supplement to prolong healthspan, establishing a scientific rationale for its application in promoting healthy aging.