學生姓名:
蘇歆惠
指導教授:
陳詠宗
學期:
114下
摘 要:
In recent years, an aging society has become a global concern, with oxidative stress and mitochondrial decline being key factors accelerating the aging process. Metabolites from microbial fermentation have attracted interest for their antioxidant properties and potential to support healthy aging. Specifically, fermented soybean by-products (FSBP), generated via a two-stage solid-state fermentation by Bacillus HHS05 and Pediococcus HHS14, significantly elevated total phenolic, flavonoid, and γ-aminobutyric acid (GABA) contents. In vivo assays in Caenorhabditis elegans demonstrated that these fermented extracts effectively extended lifespan and improved tolerance to environmental stress by lowering reactive oxygen species (ROS) and age-related lipofuscin accumulation. To elucidate the specific bioactive molecules driving these anti-aging phenotypes, untargeted metabolomic analysis was conducted, identifying a specific formononetin derivative as the critically upregulated metabolite within the FSBP. To further investigate its potential mechanisms, in silico molecular docking was performed, revealing that this formononetin derivative exhibits exceptional binding affinities with senescence associated target proteins TNF and EGFR, outperforming the known clinical inhibitors SPD304 and erlotinib. Subsequent in vivo validation confirmed that this purified derivative independently extended lifespan and promoted healthspan. Mechanistically, it exerts these effects by inhibiting the LET-23/AKT-1 signaling pathway and activating DAF-16/FOXO and SKN-1/NRF2 transcription factors, which in turn upregulate downstream stress-response genes and promote mitochondrial biogenesis. Overall, these findings suggest that both FSBP and its key formononetin derivative possess strong potential to slow aging. By improving mitochondrial function and enhancing stress resistance, they represent promising natural intervention strategies for preventing age35 related decline.
蘇歆惠.pdf