Luteolin and glycitein from Codonopsis pilosula ameliorate age-related locomotor decline in C. elegans via DAF-16-dependent but autophagy-divergent pathways

Yan Zhuang and colleagues tested three compounds isolated from Codonopsis pilosula in aged Caenorhabditis elegans. Luteolin and glycitein improved body-bend and thrashing frequencies. Both compounds reduced abnormalities in muscle structure and mitochondrial morphology. Both promoted nuclear translocation of DAF-16/FOXO. Knockdown of daf-16 abolished the locomotor benefit. The pathways then diverged. Luteolin required an lgg-1-dependent autophagy-related process. Glycitein improved locomotion without relying on the autophagic pathway. Alpha-spinasterol changed autophagosome levels but did not improve locomotor capacity. The PubMed record does not state N, doses, treatment duration, effect sizes, p values, or confidence intervals. The model is a nematode. The compounds were not tested in humans, and the study does not show improved lifespan or human healthspan. DAF-16 is a useful FOXO-related mechanism, but pathway activity in a nematode is not evidence that a supplement reproduces the effect in people. The result is a mechanistic lead. It does not support a clinical recommendation for luteolin, glycitein, or Codonopsis pilosula.

These findings elucidate the distinct pharmacological mechanisms of Codonopsis pilosula constituents, highlighting their potential as modulators of healthspan via DAF-16-dependent but mechanistically distinct pathways.