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.

玉竹已被广泛认为是一种潜在的抗衰老资源。在本研究中，我们旨在基于当前有前途的抗衰老靶点，研究植物的主要活性成分皂苷的具体作用和作用机制。结果表明，黄精皂苷 (PKS) 显着延迟应激诱导和复制细胞衰老。用 PKS 处理的模型细胞 MRC-5 表现出细胞增殖活力增加、β-半乳糖苷酶活性降低和细胞周期停滞改善。这些积极趋势归因于 PKS 对衰老相关分泌表型 (SASP) 的下调。在PKS作用下，IL-6、IL-8、CXCL-10等典型SASP因子的mRNA表达和分泌水平显着降低，有效抑制SASP介导的衰老扩散，改善细胞微环境. 此外，发现 PKS 对模型动物的健康寿命有有利影响。秀丽隐杆线虫( C. elegans)用PKS处理显示寿命延长，脂褐质积累显着减少，抗应激能力增强，抗氧化活性增强(SOD/CAT/MDA/ROS)。进一步的机制研究表明，PKS 可以上调秀丽隐杆线虫中的 sir-2.1 ，进而影响 daf-16 的转录活性。此外，PKS 表现出自噬诱导作用，自噬相关基因（lgg-1 和 bec-1）的表达上调以及在用 PKS 处理的蠕虫中监测的自噬体数量增加证明了这一点。这些发现表明PKS具有多途径抗衰老的优势。PKS作为一种很有前途的抗衰老天然药物资源，值得进一步应用和开发。