尿酸
生物
转录因子
细胞生物学
氧化应激
信号转导
下调和上调
秀丽隐杆线虫
生物化学
长寿
基因
遗传学
作者
Qin-Li Wan,Xiaodie Fu,Wenyu Dai,Jing Yang,Zhenhuan Luo,Xiao Meng,Xiao Liu,Ruowei Zhong,Hengwen Yang,Qinghua Zhou
出处
期刊:Aging
[Impact Journals, LLC]
日期:2020-02-12
卷期号:12 (3): 2840-2856
被引量:22
标识
DOI:10.18632/aging.102781
摘要
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.
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