Polygonatum kingianum saponins delay cellular senescence through SASP down-regulation and prolong the healthy lifespan of Caenorhabditis elegans by activating sir-2.1/autophagy

Polygonatum kingianum has been widely regarded as a potential resource for anti-aging. In this study, we aimed to investigate the specific effect and action mechanism of saponins, the main active component of the plant, based on the current promising anti-aging targets. The results demonstrated that Polygonatum kingianum saponins (PKS) significantly delayed stress-induced and replicative cellular senescence. Model cells MRC-5 treated with PKS exhibited increased cell proliferation viability, reduced β-galactosidase activity, and improved cell cycle arrest. These positive trends were attributed to the senescence-associated secretory phenotype (SASP) down-regulation by PKS. The mRNA expression and factor secretion levels of some typical SASP factors, such as IL-6, IL-8, and CXCL-10, were significantly decreased under the effect of PKS, which effectively inhibited SASP-mediated senescence diffusion and improved the cellular microenvironment. Additionally, PKS was found to have a favorable effect on the healthy lifespan of model animals. Caenorhabditis elegans (C. elegans) treated with PKS showed increased lifespan, a significant reduction in lipofuscin accumulation, strengthened stress resistance ability, and enhanced antioxidant activity (SOD/CAT/MDA/ROS). Further mechanistic studies indicated that PKS can upregulate sir-2.1 in C. elegans and then affect the transcriptional activity of daf-16. Moreover, PKS exhibited autophagy-inducing effects, as evidenced by the up-regulated expression of autophagy-related genes (lgg-1 and bec-1) and an increased number of autophagosome monitored in worms treated with PKS. These findings suggest that PKS possesses the superiority of multiple pathways for anti-aging. As a promising anti-aging natural drug resource, PKS is worthy of further application and development.