Bridging traditional knowledge and modern discovery: The role of zebrafish in anti-aging research of medicinal and edible traditional Chinese medicine.

BACKGROUND: With the acceleration of global aging, anti-aging research has become a critical frontier in the life sciences. The zebrafish (Danio rerio), as a well-established model organism, offers exceptional advantages for anti-aging studies owing to its high genetic and physiological homology with humans, evolutionarily conserved aging mechanisms, suitability for high-throughput screening, and capacity to model telomere dynamics. Concurrently, Traditional Chinese Medicine (TCM) offers a holistic perspective on aging, attributing it to systemic imbalances such as deficiency of visceral function, qi-blood disharmony, and yin-yang imbalance. Within this framework, medicinal and edible TCM-natural substances recognized for both nutritional and therapeutic value-have shown considerable promise in mitigating aging-related processes, supported by their favorable safety profiles and historical documentation.

METHODS: This review systematically collates and analyzes recent advances in the application of zebrafish as a model organism for evaluating the anti-aging efficacy of medicinal and edible TCM. Literature published up to September 2023 was retrieved from databases such as PubMed, Web of Science, and Scopus using keywords including "zebrafish," "anti-aging," "medicinal and edible herbs," and "traditional Chinese medicine." Data on aging models, mechanistic pathways, and phytochemical activities were extracted and synthesized to elucidate the synergistic potential of zebrafish and TCM in gerontological research.

RESULTS: A total of 978 publications were identified using the keywords related to "anti-aging" and "medicinal and edible herbs." Subsequently, 135 relevant studies were selected for this review based on the use of zebrafish models and aging-related indicators.This review focuses on the establishment of zebrafish aging models and the evaluation of anti-aging effects of medicinal and edible traditional Chinese medicines in these models. Three major types of zebrafish aging models were identified, including chemically induced models, genetically modified models, and natural aging models, which collectively reproduced key aging-related features such as oxidative stress, DNA damage, telomere attrition, apoptosis, and cellular senescence. The medicinal and edible TCMs reviewed showed anti-aging potential mainly through enhancing antioxidant defense, modulating immune and inflammatory responses, and regulating senescence-related signaling pathways. Representative substances, including Astragalus membranaceus, Lycium barbarum, and Panax ginseng, were reported to improve aging-related phenotypes in zebrafish by increasing antioxidant enzyme activities, reducing lipid peroxidation, and modulating p53-/telomerase-associated pathways. These findings support the value of zebrafish as an efficient in vivo platform for screening and mechanistic investigation of anti-aging natural products.

CONCLUSION: The integration of zebrafish models with medicinal and edible TCM research provides a powerful platform for identifying anti-aging compounds and deciphering their mechanisms of action. Despite certain limitations-such as a relatively long natural lifespan and environmental sensitivity-zebrafish offer unique advantages in telomere biology, regenerative capacity, and experimental scalability. Future studies should focus on elucidating the complex interactions among TCM compounds, optimizing model applicability, and validating findings in higher vertebrates. Through interdisciplinary collaboration, the combination of zebrafish and TCM holds promise for developing safe, effective, and naturally derived anti-aging interventions.