Abstract
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.
Highlights
The process of aging has fascinated humankind for thousands of years
Our results from this study indicated that uric acid significantly extended the life span, delayed age-related physiological functions, and enhanced oxidative stress resistance in C. elegans by activating the stress-related transcription factors DAF16/FOXO and SKN-1/NRF2 and by regulating the insulin/IGF-1 signaling (IIS) and reproductive signaling pathways
We found that treatment with 2 mM uric acid significantly protected animals against oxidative stress, indicating that uric acid has antioxidant activity (Figure 1B, Supplementary Figure 1, Supporting information)
Summary
The process of aging has fascinated humankind for thousands of years. Aging has been defined as a synchronous global decline in physiological and psychological function, accompanied by many diseases, including type 2 diabetes, cancer and hypertension [1, 2]. One of the main mechanisms underlying aging and age-associated disease is a chronic elevation of reactive oxygen species (ROS) [3] It has been nearly 50 years since Harman proposed the “free radical theory” of aging [4]. Several important defense mechanisms in the body (i.e., ROS scavengers, protein repair, refold machinery and molecular degradation apparatuses) are regulated to maintain ROS www.aging-us.com homeostasis in the body. When these defense mechanisms are compromised, ROS levels are elevated to excess and are responsible for the processing of aging [5, 6]. In addition to these two compounds, some antioxidants that can affect life span and health span have been discovered, such as melatonin [9], hydralazine [10], cytoprotective polyphenol [11], peptides [12] and polysaccharides [13], which help alleviate oxidative stress and delay aging
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
