Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants.
Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants.
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DOI：
10.18632/aging.100275
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Ayyadevara S
中科院分区：
文献类型：
--
作者：
Shmookler Reis RJ;Xu L;Lee H;Chae M;Thaden JJ;Bharill P;Tazearslan C;Siegel E;Alla R;Zimniak P;Ayyadevara S
许多寿命调节基因参与氧化底物和最终产物的产生，或它们的解毒和去除。在这些代谢物中，只有过氧化物具有产生自由基链式反应的能力。在这项研究中，脂肪酸谱在一组秀丽隐杆线虫突变体中进行了比较，这些突变体在统一的遗传背景下跨越了10倍的寿命范围。两种脂质结构特性与这些蠕虫的寿命密切相关：在寿命最长的突变体中，脂肪酸链长度和对氧化的敏感性都急剧下降（影响胰岛素样信号通路）。这提示了一个功能模型，其中长寿受益于脂质过氧化底物的减少，被脂肪酸链长度的协调下降所抵消，以维持膜的流动性。该模型通过破坏脂质生物合成的潜在步骤进行测试，使用RNAi敲低来消耗参与脂肪酸代谢的基因转录本。这些干预措施对寿命产生的影响与产品的功能和丰度完全一致。大多数基因敲低也对过氧化氢应激的生存产生一致的影响，过氧化氢应激可引发脂过氧化物连锁反应。
Many lifespan-modulating genes are involved in either generation of oxidative substrates and end-products, or their detoxification and removal. Among such metabolites, only lipoperoxides have the ability to produce free-radical chain reactions. For this study, fatty-acid profiles were compared across a panel of C. elegans mutants that span a tenfold range of longevities in a uniform genetic background. Two lipid structural properties correlated extremely well with lifespan in these worms: fatty-acid chain length and susceptibility to oxidation both decreased sharply in the longest-lived mutants (affecting the insulinlike-signaling pathway). This suggested a functional model in which longevity benefits from a reduction in lipid peroxidation substrates, offset by a coordinate decline in fatty-acid chain length to maintain membrane fluidity. This model was tested by disrupting the underlying steps in lipid biosynthesis, using RNAi knockdown to deplete transcripts of genes involved in fatty-acid metabolism. These interventions produced effects on longevity that were fully consistent with the functions and abundances of their products. Most knockdowns also produced concordant effects on survival of hydrogen peroxide stress, which can trigger lipoperoxide chain reactions.
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影响因子：
7.8
作者：
Ayyadevara S;Tazearslan C;Bharill P;Alla R;Siegel E;Shmookler Reis RJ
通讯作者：
Shmookler Reis RJ
影响因子：
--
作者：
Corella, Dolores;Peloso, Gina;Arnett, Donna K.;Demissie, Serkalem;Cupples, L. Adrienne;Tucker, Katherine;Lai, Chao-Qiang;Parnell, Laurence D.;Coltell, Oscar;Lee, Yu-Chi;Ordovas, Jose M.
通讯作者：
Ordovas, Jose M.
影响因子：
3.7
作者：
Brooks KK;Liang B;Watts JL
通讯作者：
Watts JL
秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
影响因子：
4.5
作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
通讯作者：
Watts, Jennifer L.
一种迭代的块移动方法，用于保留时间比对，可保留气相色谱 - 质谱峰的形状和面积。
影响因子：
3
作者：
Chae, Minho;Reis, Robert J. Shmookler;Thaden, John J.
通讯作者：
Thaden, John J.