Aging-modulatory effects of Pausinystalia macroceras (K. Schum.) Pierre polysaccharides are associated with DAF-16/FOXO and SKN-1/Nrf2 signaling in multiple aging models.

With the global aging population and increasing burden of age-related diseases, delaying aging and maintaining healthspan(definition) have become important research priorities. Aging is a complex biological process involving progressive declines in physiological function, stress resistance, proteostasis(definition), and metabolic homeostasis, driving the development of aging modulators that target conserved longevity-associated pathways. Although pharmacological and natural aging modulators have attracted growing attention, concerns regarding the long-term safety and clinical applicability of pharmacological interventions, together with the incompletely understood mechanisms of many natural modulators, remain. Plant-derived polysaccharides are promising natural aging modulators owing to their favorable biocompatibility, low toxicity, and diverse biological activities, but their aging-modulatory effects and underlying mechanisms remain insufficiently explored. In this study, Pausinystalia macroceras (K. Schum.) Pierre polysaccharides (PMP) were found to exhibit aging-modulatory effects in both Caenorhabditis elegans and Drosophila melanogaster aging models. PMP delayed the progression of aging by extending lifespan, preserving healthspan-associated functions, and maintaining physiological fitness without adversely affecting growth, feeding behavior, or reproductive capacity. PMP also enhanced resilience to diverse environmental stresses and attenuated age-associated physiological deterioration. At the cellular level, PMP maintained redox and proteostasis homeostasis by reducing intracellular reactive oxygen species accumulation, lipofuscin deposition, and polyglutamine aggregation. These protective effects were associated with enhanced DAF-16/FOXO- and SKN-1/Nrf2-mediated longevity and stress-response signaling, accompanied by increased downstream antioxidant defenses, including SOD-3 and GST-4. PMP further alleviated age-associated metabolic disturbances by modulating amino acid, carbohydrate, and energy metabolism, indicating its ability to preserve metabolic homeostasis during aging. Overall, PMP delays aging progression in association with coordinated regulation of longevity signaling, stress resistance, proteostasis, and metabolic homeostasis, providing a mechanistic basis for its development as a natural aging-modulatory agent.