Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension.
Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension.
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DOI：
10.1007/s11306-013-0608-8
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发表时间：
2014-08-01
期刊：
影响因子：
3.6
通讯作者：
Siuzdak, Gary
中科院分区：
文献类型：
--
作者：
Patti, Gary J.;Tautenhahn, Ralf;Johannsen, Darcy;Kalisiak, Ewa;Ravussin, Eric;Bruening, Jens C.;Dillin, Andrew;Siuzdak, Gary
在多细胞模式生物如秀丽隐杆线虫中，不同信号通路和转录因子的操纵已显示出以细胞非自主的方式影响寿命。这些数据表明，整个有机体衰老的协调涉及内分泌信号，然而，这些信号的分子身份尚未确定，其在人类中的潜在相关性是未知的。在这里，我们描述了一种新的代谢组学方法，以确定分子直接与延长寿命的C。代表与年龄相关的内分泌信号的候选化合物。为了确定与寿命直接相关的代谢扰动，我们开发了代谢组学软件进行荟萃分析，使多个不同的突变体的智能比较。将长寿的GLP-1、DAF-2和ISP-1突变体与它们各自的对照进行简单的成对比较，发现了超过11，000个具有统计学意义的失调代谢物特征。通过使用荟萃分析，我们能够将这个数字减少到六种最有可能与延长寿命相关的化合物。基于质谱的成像研究表明，这些代谢物可能定位于C。肌肉我们通过比较年轻人和老年人的四头肌组织，将代谢组学分析扩展到人类，发现与蠕虫寿命相关的两种相同化合物也随着年龄的增长而在人类肌肉中发生变化。这些发现提供了可能作为年龄相关内分泌信号的候选化合物，并暗示肌肉是调节其在人类中水平的潜在组织。
The manipulation of distinct signaling pathways and transcription factors has been shown to influence life span in a cell-non-autonomous manner in multicellular model organisms such as Caenorhabditis elegans. These data suggest that coordination of whole-organism aging involves endocrine signaling, however, the molecular identities of such signals have not yet been determined and their potential relevance in humans is unknown. Here we describe a novel metabolomic approach to identify molecules directly associated with extended life span in C. elegans that represent candidate compounds for age-related endocrine signals. To identify metabolic perturbations directly linked to longevity, we developed metabolomic software for meta-analysis that enabled intelligent comparisons of multiple different mutants. Simple pairwise comparisons of long-lived glp-1, daf-2, and isp-1 mutants to their respective controls resulted in more than 11,000 dysregulated metabolite features of statistical significance. By using meta-analysis, we were able to reduce this number to six compounds most likely to be associated with life-span extension. Mass spectrometry-based imaging studies suggested that these metabolites might be localized to C. elegans muscle. We extended the metabolomic analysis to humans by comparing quadricep muscle tissue from young and old individuals and found that two of the same compounds associated with longevity in worms were also altered in human muscle with age. These findings provide candidate compounds that may serve as age-related endocrine signals and implicate muscle as a potential tissue regulating their levels in humans.
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影响因子：
3.3
作者：
Patti, G. J.;Shriver, L. P.;Wassif, C. A.;Woo, H. K.;Uritboonthai, W.;Apon, J.;Manchester, M.;Porter, F. D.;Siuzdak, G.
通讯作者：
Siuzdak, G.
影响因子：
64.8
作者：
Herndon, LA;Schmeissner, PJ;Driscoll, M
通讯作者：
Driscoll, M
影响因子：
56.9
作者：
Arantes-Oliveira, N;Apfeld, J;Kenyon, C
通讯作者：
Kenyon, C
影响因子：
64.5
作者：
Durieux J;Wolff S;Dillin A
通讯作者：
Dillin A
DOI：
10.1073/pnas.0405775102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Broughton, SJ;Piper, MDW;Partridge, L
通讯作者：
Partridge, L