Research On The Anti-Aging Effect And Mechanism Of Uric Acid In C.elegans

Objective: In this study,we used Caenorhabditis elegans(C.elegans)as the model organism.First of all,we screened some compounds and found that uric acid have anti-aging effect,and then,we used the nematode strains with different mutations or GFP to explore the mechanism of lifespan extension by uric acid,then found the mechanism of delaying aging induced by uric acid.Methods: The compound is dissolved in water to make a stable solution.Add the solution to the NGM plate.The nematodes were raised on the NGM plate for treating with drugs.First,the antioxidative of uric acid was tested to verify that uric acid can play the antioxidant activity in C.elegans.Then,the nematodes were treated with different concentrations of uric acid,we observed the lifespan changes of the treated or untreated animals,and we finally found the concentration with the best effect on lifespan extension.Then,through the treatment of different mutant strains with uric acid,after results analysis,we found possible related signals pathways,and then performed uric acid treatment and analysis to the related nematode strains,verify the possibility of the pathway.Results: In this study,we screened compounds in C.elegans and found that the end product of purine metabolism in the human body,uric acid,can enhances the resistance of oxidative stress and prolong the lifespan of C.elegans.Uric acid enhances a variety of aging pathways,and leads to the upregulation of genes that are required for life span extension,ultimately,extending the lifespan of nematodes.We found that the transcription factors,DAF-16/FOXO,SKN-1/NRF2,and HSF-1,contribute to the longevity beneficially by uric acid.Our results also show that uric acid induced lifespan extension by regulating the reproductive signals and the insulin/IGF-1 signaling(IIS)pathway.In addition,we also found that the mitochondrial function plays an important role in uric acid-mediated lifespan extension.Conclusions: In summary,our data indicate that the end product of purine metabolism inthe human body,uric acid,can prolongs the lifespan of C.elegans,in part because of its antioxidative activity,which in turn adjusts IIS and reproductive signaling pathways,thereby activating transcription factors DAF-16,HSF-1,and SKN-1,ultimately,extending the lifespan of C.elegans.