Anti-aging effects of low-molecular-weight polysaccharide PSP-1-1 from steamed Polygonatum sibiricum via gut...

The rising prevalence of aging-associated chronic conditions underscores the need for interventions that promote healthy aging. In this study, a low-molecular-weight polysaccharide (PSP-1-1, 2.7 kDa) was isolated from steamed Polygonatum sibiricum using bioactivity-guided purification and structurally characterized as a branched β-(1 → 4)-galactan with C-6 substitutions. Using Caenorhabditis elegans, PSP-1-1 demonstrated significant anti-aging effects and neuroprotective activities. Our results showed that PSP-1-1 (100 μg/mL) significantly delayed Aβ-induced paralysis of CL4176 worms, the value of PT₅₀ was increased by 51.42% (p < 0.001), and it extended the median lifespan of wild-type N2 nematodes by 29.88% (p < 0.001). PSP-1-1 also markedly enhanced oxidative stress resistance, and reduced intracellular reactive oxygen species (ROS) levels by 21.36%. Moreover, we found PSP-1-1 treatment modulated the human gut microbiota, increasing the ratio of Firmicutes and enhancing the abundance of beneficial short-chain fatty acid (SCFA)-producing bacteria, such as Lactobacilli. These findings underscore the potential of PSP-1-1 as a natural therapeutic agent for healthy aging and neuroprotection.