Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model.
Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model.
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DOI：
10.1186/1741-7007-10-67
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发表时间：
2012-07-31
期刊：
影响因子：
5.4
通讯作者：
Weinkove D
中科院分区：
文献类型：
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作者：
Virk B;Correia G;Dixon DP;Feyst I;Jia J;Oberleitner N;Briggs Z;Hodge E;Edwards R;Ward J;Gems D;Weinkove D
肠道微生物影响动物健康，因此是减缓衰老干预措施的潜在目标。活的大肠大肠杆菌为线虫提供了重要的微量营养素，如动物不能合成的叶酸。然而，这种微生物也限制了C。elegans寿命。了解这些相互作用可能有助于了解肠道微生物如何影响哺乳动物衰老。偶然的，我们分离出了一个E。大肠杆菌突变体，减缓C. elegans老化我们鉴定出被破坏的基因是aroD，这是微生物合成芳香族化合物所必需的。向培养基中添加芳香族化合物显示增加的C。线虫的寿命是由叶酸的前体对氨基苯甲酸的可用性降低引起的。与此结果一致，磺胺甲恶唑（一种磺胺）抑制叶酸合成导致C。elegans寿命。正如预期的那样，这些治疗引起细菌和蠕虫叶酸水平的降低，如通过完整叶酸的质谱法所测量的。叶酸循环是细胞生物合成所必需的。然而，细菌增殖和C.在增加寿命的条件下，秀丽线虫的生长和繁殖不受影响。在这种动物中：微生物系统中，叶酸超过了生物合成所需的量。这项研究表明，微生物叶酸合成是一个可以减缓动物衰老的目标，而不会产生有害影响。
Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging. Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan. In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.
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影响因子：
3.2
作者：
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通讯作者：
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DOI：
10.1016/j.jasms.2007.01.017
发表时间：
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影响因子：
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影响因子：
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作者：
通讯作者：
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影响因子：
9.9
作者：
通讯作者：
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