Puerarin extends lifespan and enhances the resistance to oxidative stress through AMPK/TFEB mediated autophagy in Caenorhabditis elegans.

Lingjie Meng, Yang Liu, Xiaocong Li, Xin Xiao, Xinyi Du, Fang Liu, Yi Xiao

Institute of Life Sciences, Zunyi Medical University, Zunyi Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi Guizhou 563000, China; The Key Laboratory of Pharmaceutical Research for Tumor Prevention and Treatment of the Education Department of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China. Electronic address: [email protected] of Life Sciences, Zunyi Medical University, Zunyi Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi Guizhou 563000, China; The Key Laboratory of Pharmaceutical Research for Tumor Prevention and Treatment of the Education Department of Guizhou Province, Zunyi Medical University, Zunyi Guizhou 563000, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

As the aging population increases, exploring effective strategies to delay aging and promote healthy longevity has become a crucial topic in the life sciences. Puerarin (PUE) is a natural isoflavone derivative derived from Pueraria lobata, a plant widely recognized for its dual role as both a food and a medicinal herb. While PUE is known for its diverse pharmacological properties, its role in aging regulation and the associated molecular mechanisms are not yet fully elucidated. In this study, we found that PUE markedly extends the healthy lifespan of Caenorhabditis elegans and mitigates aging-related phenotypes, including lipofuscin accumulation and decreased locomotor capacity. Through genetic screening and functional validation, we demonstrated that PUE facilitates the nuclear translocation of the transcription factor HLH-30 (the mammalian homolog of TFEB) in an AMPK-dependent manner, thereby regulating autophagy. Importantly, this autophagic response was essential for the lifespan-extending effects of PUE. Additionally, PUE enhanced the oxidative stress resistance of C. elegans via the AMPK-TFEB signaling pathway, an effect characterized by reduced reactive oxygen species (ROS) accumulation and increased activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione (GSH). The findings establish a mechanistic rationale for applying PUE in aging delay and age-related disease prevention and underscore the potential significance of medicinal food plants in developing anti-aging strategies.

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Research summary

Puerarin extends the lifespan and healthspan of Caenorhabditis elegans by activating the AMPK/TFEB-mediated autophagy pathway to reduce oxidative stress. This study represents a standard, incremental pharmacological screen in a model organism, lacking the novelty or mechanistic depth required for high impact, and while it addresses aging mechanisms, it does not solve root causes of aging in a transformative way.

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