Molecular pathways related to the longevity promotion and cognitive improvement of Cistanche tubulosa in Drosophila

Background: The aging process, including physical dysfunction and age-related memory impairment (AMI), are considered to be correlated with cumulative oxidative damages and insulin/IGF-1 signaling pathway. Purpose: The present study was to elucidate the in vivo effects on delaying aging and ameliorating AMI and underlying molecular mechanisms of Cistanche tubulosa (CT), a herb used in traditional Chinese medicine to improve sexual function and treat kidney dysfunction. Methods: The flies, treated and untreated with CT, were observed for lifespan, resistance to oxidative stress with H2O2 or paraquat, starvation assay, cognitive behaviors with T-maze, and transcript levels of target genes with quantitative RT-PCR. Results: Administering CT extended the mean and maximum lifespan and increased resistance to oxidative stress in flies. CT supplementation also enhanced memory formation in young flies and suppressed AMI upon aging. Several genes and signaling pathways, including the mechanistic target of rapamycin (mTOR) and Notch networks, have been identified as causing these pharmacological effects and alterations in the gene expression of glutamate receptors. Conclusion: Our results indicate that CT supplementation may contribute to slowing aging phenotypes and alleviating cognitive behavioral decline in flies, indicating potential applicability for enhancing human health and reducing susceptibility to age-related disorders.