Abstract

Astragalus polysaccharide (APS) is a notable bioactive component of Astragalus membranaceus and has been extensively investigated for its pharmacological activities, including antioxidant, neuroprotection, and anticancer effects. However, the beneficial effects and mechanisms of APS on anti-aging diseases remain largely unknown. Here, we utilized the classic model organism Drosophila melanogaster to investigate the beneficial effects and mechanism of APS on aging-related intestinal homeostasis imbalance, sleeping disorders, and neurodegenerative diseases. The results showed that administration of APS significantly attenuated age-associated disruption of the intestinal barrier, loss of gastrointestinal acid-base balance, reduction in intestinal length, overproliferation of the intestinal stem cells (ISCs), and sleeping disorders upon aging. Furthermore, APS supplementation delayed the onset of Alzheimer's phenotypes in Aβ42-induced Alzheimer's disease (AD) flies, including the extension of lifespan and the increase in motility, but without rescuing neurobehavioral deficits in the AD model of taupathy and Parkinson's disease (PD) model of Pink1 mutation. In addition, transcriptomics was used to dissect updated mechanisms of APS on anti-aging, such as JAK-STAT signaling, Toll signaling, and IMD signaling pathways. Taken together, these studies indicate that APS plays a beneficial role in modulating aging-related diseases, thereby as a potential natural drug to delay aging.