独特的代谢组学特征与人类长寿相关。
Distinct metabolomic signatures are associated with longevity in humans.
作者信息
Cheng Susan, Larson Martin G, McCabe Elizabeth L, Murabito Joanne M, Rhee Eugene P, Ho Jennifer E, Jacques Paul F, Ghorbani Anahita, Magnusson Martin, Souza Amanda L, Deik Amy A, Pierce Kerry A, Bullock Kevin, O'Donnell Christopher J, Melander Olle, Clish Clary B, Vasan Ramachandran S, Gerszten Robert E, Wang Thomas J
机构信息
Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (SC, MGL, JMM, JEH, CJO, RSV, TJW); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (SC); Department of Mathematics and Statistics, Boston University, Boston, MA (MGL); Department of Biostatistics, Boston University School of Public Health, Boston, MA (ELM); Cardiology Division (JEH, AG, CJO, REG), Cardiovascular Research Center (REG), and Renal Division (EPR), Massachusetts General Hospital, Harvard Medical School, Boston, MA; General Internal Medicine (JMM), Cardiology (JEH, RSV), and Preventive Medicine (RSV), Department of Medicine, Boston University School of Medicine, Boston, MA; Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA (PFJ); Department of Clinical Sciences, Lund University, Malmö (MM, OM); Broad Institute of MIT and Harvard, Cambridge, MA (ALS, AAD, KAP, KB, CBC, REG); National Heart, Lung & Blood Institute Division of Intramural Research, Bethesda, MD (CJO); and, Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (TJW).
出版信息
Nat Commun. 2015 Apr 13;6:6791. doi: 10.1038/ncomms7791.
Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death.
新陈代谢的改变会影响实验模型中的寿命，但人类方面的数据尚缺。在此，我们使用液相色谱/质谱法对217种血浆代谢物进行定量，并在长达20年随访的一大群男性和女性中研究它们与长寿的关系。我们发现，柠檬酸循环中间体异柠檬酸和胆汁酸牛磺胆酸盐的浓度较高，与达到80岁的长寿几率较低相关。异柠檬酸浓度较高，但牛磺胆酸盐并非如此，其在基线时也与较差的心血管健康以及未来心血管疾病和死亡风险相关。所鉴定的代谢物均与癌症风险无关。我们的研究结果表明，一些但并非所有与人类长寿相关的代谢途径都与常见死因的风险有关。
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