Liu Jun Zi Decoction extends lifespan and healthspan through p16/p21 signaling in Caenorhabditis elegans

Age-related functional decline has emerged as a major challenge to human health and societal development. Safe and effective anti-aging interventions, particularly those involving natural products, offer promising strategies to delay aging and promote healthy longevity. In this study, we used Caenorhabditis elegans (C. elegans) models to investigate the anti-aging effects and underlying mechanisms of Liu Jun Zi Decoction (LJZD), a traditional Chinese herbal formula. The results showed that LJZD extended lifespan and enhanced stress resistance and locomotion in C. elegans. Serum pharmacochemistry, network pharmacology, and molecular docking identified key bioactive compounds that target the IIS/mTOR and p16/p21 pathways. Furthermore, we found that LJZD promoted longevity by improving mitochondrial function via the IIS-mTOR axis. Notably, LJZD also conferred neuroprotection in Aβ-/tau-expressing models. These findings provide mechanistic insights into multi-target herbal interventions for aging and neurodegeneration.