Research Paper Volume 12, Issue 3 pp 2840—2856
Uric acid induces stress resistance and extends the life span through activating the stress response factor DAF-16/FOXO and SKN-1/NRF2
- 1 Zhuhai Precision Medical Center, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Guangdong 510632, Guangzhou, China
- 2 The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangdong 510632, Guangzhou, China
- 3 Qingyuan People's Hospital, The Six Affiliated Hospital of Guangzhou Medical University, Guangdong 511518, Qingyuan, China
- 4 Internship Program, The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangdong, 510632, Guangzhou, China
received: August 17, 2019 ; accepted: January 19, 2020 ; published: February 12, 2020 ;https://doi.org/10.18632/aging.102781
How to Cite
Copyright © 2020 Wan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uric acid is a common metabolite found in mammals’ serum. Recently, several metabolites have been identified that modulate aging, and uric acid levels are positively correlated with mammals’ lifespan. However, the molecular mechanisms underlying this are largely undefined. Here we show that uric acid, an end product of purine metabolism, enhances the resistance of oxidative stress and extends the life span of Caenorhabditis elegans (C. elegans). We show that uric acid enhances a variety of pathways and leads to the upregulation of genes that are required for uric acid-mediated life span extension. We find that the transcription factors DAF-16/FOXO, SKN-1/NRF2 and HSF-1 contribute to the beneficial longevity conferred by uric acid. We also show that uric acid induced life span extension by regulating the reproductive signaling and insulin/IGF-1 signaling (IIS) pathways. In addition, we find that mitochondrial function plays an important role in uric acid-mediated life span extension. Taken together, these data suggest that uric acid prolongs the life span of C. elegans, in part, because of its antioxidative activity, which in turn regulates the IIS and the reproductive signaling pathways, thereby activating the function of the transcription factors DAF-16, HSF-1 and SKN-1.