Baicalein Enhances Longevity and Healthspan of C. elegans Through the Insulin/IGF‐1 Signaling Pathway

ABSTRACT Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis , possesses notable anti‐inflammatory, antioxidative, and anticancer properties. Despite its therapeutic potential, the full scope of its effects on healthspan(definition) and longevity remains unexplored. This study investigates the impact of baicalein on longevity and health‐related biomarkers using the nematode Caenorhabditis elegans . Baicalein was administered to a wild‐type N2 strain, seven mutant strains, and three reporter strains. Its influence on longevity, motility, lipofuscin accumulation, and oxidative stress resistance was assessed. The methodology included Kaplan–Meier survival analysis, in vivo imaging, fluorescence microscopy, and real‐time PCR to evaluate RNA and protein expression. The findings indicate that baicalein significantly extends lifespan and enhances health markers, including improved motility, increased oxidative stress resistance, and reduced lipofuscin accumulation. Mechanistically, baicalein suppressed the DAF‐2‐mediated insulin/IGF‐1 signaling pathway and promoted the nuclear translocation of DAF‐16, a pivotal longevity transcription factor. Furthermore, baicalein upregulated the expression of the sod‐3 gene, which is associated with enhanced stress tolerance and lifespan extension. These results elucidate the function of baicalein in promoting longevity and healthspan in C. elegans through modulation of insulin/IGF‐1 signaling. Future studies are warranted to explore the applicability of baicalein in human aging to pave the way for innovative antiaging supplement formulations.