Bound polyphenols from carrot dietary fiber delay aging in Caenorhabditis elegans through the IIS pathway and metabolic remodeling

Abstract

Polyphenols are a class of plant-derived phytochemicals with potent antioxidant and anti-aging activities. However, current research has largely focused on free polyphenols, whereas dietary fiber-associated bound polyphenols remain insufficiently explored. In this study, bound polyphenols from carrot dietary fiber, referred to as CDF-BP, were investigated for their anti-aging activity in Caenorhabditis elegans. At 50 μg mL⁻¹, CDF-BP extended mean lifespan by 25.58% and improved healthspan, as reflected by enhanced motility and reduced lipofuscin accumulation and lipid deposition. Integrated multi-omics analysis revealed that these effects were driven by coordinated signaling and metabolic remodeling. Transcriptomic profiling and validation assays showed that CDF-BP modulated insulin/IGF-1 signaling and induced stress response genes associated with DAF-16 and SKN-1, including sod-3 and gst-4. In parallel, non-targeted metabolomics revealed broad metabolic remodeling suggestive of metabolic reallocation. CDF-BP shifted lipid metabolism from storage toward utilization, as indicated by activation of the carnitine shuttle through elevated acylcarnitines, and was associated with enhanced xenobiotic response pathways. Genetic analyses using daf-2, daf-16, and skn-1 mutants confirmed that the effects of CDF-BP on promoting longevity depended on these pathways. Collectively, these findings identify CDF-BP as a bioactive modulator of longevity that acts through convergent regulation of stress response signaling and metabolic reprogramming, and further suggest that bound polyphenols may represent an underestimated target in nutritional strategies for healthy aging.