Abstract
With the global rise in aging populations and age-related diseases, the demand for safe and effective aging modulatory interventions is steadily increasing. Although several clinical drugs have shown aging modulatory potential, their long-term efficacy and safety remain major concerns. Plant-derived polysaccharides, known for their ability to modulate multiple longevity-related signaling pathways, have emerged as promising natural candidates due to their high biocompatibility and low toxicity. However, their underlying mechanisms remain insufficiently explored, limiting their translational potential. This study identified a novel aging modulatory intervention based on Eurycoma longifolia Jack polysaccharides (ELP) and systematically evaluated its effects in two established aging models, C. elegans and D. melanogaster. ELP significantly extended lifespan and healthspan in both models. Mechanistically, it reduced age-associated lipofuscin accumulation and polyglutamine aggregation, activated the conserved IIS/DAF-16 signaling pathway, and enhanced cellular defense by regulating antioxidant enzymes. Furthermore, metabolomic analysis revealed that ELP restored metabolic homeostasis by modulating key amino acid, carbohydrate, and lipid metabolic networks. Collectively, this study not only reveals a new natural aging modulatory intervention but also provides comprehensive mechanistic insights, supporting the future development of ELP as a safe and effective nutraceutical or therapeutic agent for mitigating age-related functional decline.
