Crassifolin A prolongs lifespan and healthspan in Caenorhabditis elegans via activating autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE

The root of Croton crassifolius Geiseler (C. crassifolius), commonly known as "Jiguxiang" in traditional Chinese medicine, is globally recognized for its ethnomedical applications in treating a spectrum of diseases. Crassifolin A (CA), a diterpenoid compound extracted from the roots of C. crassifolius, exhibits anti-herpes simplex virus (HSV), anti-viral and anti-angiogenic properties.

AIM OF THE REVIEW

This study aimed to explore the effects of CA on aging and the mechanisms involved.

MATERIALS AND METHODS

Utilizing Caenorhabditis elegans (C. elegans) as a model organism, we conducted a comprehensive survival analysis and evaluated aging-related phenotypes, including the period of fast body movement and body bending rates. To elucidate the molecular mechanisms of CA's impact on aging, we employed a multifaceted approach, including reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, and fluorescence quantification of transgenic reporter strains.

RESULTS

Our findings demonstrated that CA significantly prolonged both the lifespan and healthspan of C. elegans. The survival benefits conferred by CA were found to correlate with the activation of several key aging-related signaling pathways, including insulin/insulin-like signaling pathway (IIS), dietary restriction (DR) pathway, and germline signaling pathway. Engagement of these pathways led to the activation of transcription factors DAF-16/FOXO, SKN-1/NRF2, HSF-1 and HLH-30/TFEB, as well as the nuclear receptor DAF-12. Consequently, this activation cascade prompted an upregulation of autophagy, a cellular process associated with the maintenance of cellular homeostasis and longevity.

CONCLUSION

Our study delineates novel mechanisms underlying anti-aging strategies, establishing a conceptual framework for the exploitation and advancement of traditional Chinese medicinal herbs as potential therapeutic agents in the fight against aging and its associated pathologies.