Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans.
Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans.
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与秀丽隐杆线虫生殖调节衰老相关的代谢组学特征
DOI：
10.18632/aging.101170
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发表时间：
2017-02-06
期刊：
影响因子：
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通讯作者：
Luo HR
中科院分区：
文献类型：
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作者：
Wan QL;Shi X;Liu J;Ding AJ;Pu YZ;Li Z;Wu GS;Luo HR
在秀丽隐杆线虫（C. elegans）中，生殖干细胞（GSCs）的消融会导致不育，同时寿命延长。据报道，衰老和生殖都与新陈代谢有着千丝万缕的联系。然而，很少有研究探讨极性小分子代谢在生殖调控寿命方面的作用。在这项工作中，我们结合核磁共振（NMR）和超高效液相色谱 - 质谱联用（UPLC - MS）技术对秀丽隐杆线虫的水溶性代谢组进行了分析。通过比较不同突变体在两个生理年龄之间的代谢指纹，我们的结果表明，衰老的特征是代谢组重塑和代谢衰退。此外，通过分析长寿的无生殖细胞的glp - 1突变体的代谢谱，我们发现glp - 1突变体调节许多随年龄变化的代谢物水平以延缓衰老，包括嘧啶和嘌呤代谢中间产物浓度升高以及柠檬酸循环中间产物浓度降低。有趣的是，通过分析daf - 16；glp - 1双突变体的代谢组，我们的结果显示，一些有助于生殖细胞介导的长寿的代谢交换是由转录因子FOXO/DAF - 16介导的，包括嘧啶代谢和三羧酸循环。基于全面的代谢分析，我们对秀丽隐杆线虫中由生殖细胞信号调控的寿命和代谢之间的关系提供了新的见解。
In Caenorhabditis elegans (C. elegans), ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans. Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans