Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Aging Cell. 2012 Dec;11(6):960-7. doi: 10.1111/j.1474-9726.2012.00865.x. Epub 2012 Aug 27.
Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32-81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10(-04) to 7.8 × 10(-42) , α(corr) = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging.
了解衰老的复杂性至关重要。目前,代谢组学为解决这一问题提供了新颖而强大的方法。然而,迄今为止,仅有少数基于大样本的代谢研究。在此,我们提供了关于人类内稳定状态与年龄相关的代谢物浓度变化的新的、具体的信息。我们报告了两项基于人群的研究结果:来自德国的 KORA F4 研究作为发现队列,其中包括 1038 名女性和 1124 名男性参与者(32-81 岁),以及 TwinsUK 研究作为复制队列,其中包括 724 名女性参与者。通过 FIA-MS/MS 对空腹血清样本进行靶向代谢组学分析,共定量了 131 种代谢物。其中,71/34 种代谢物在女性/男性中与年龄显著相关(BMI 调整后)。我们进一步在女性中确定了一组 13 种独立的代谢物(P 值范围为 4.6×10(-04)至 7.8×10(-42),α(corr) = 0.004)。这 13 种代谢物中有 11 种在 TwinsUK 研究中得到了复制,其中包括 7 种随年龄增长而增加的代谢物浓度(C0、C10:1、C12:1、C18:1、SM C16:1、SM C18:1 和 PC aa C28:1),而组氨酸则减少。这些结果表明代谢谱与年龄相关,可能反映了不同的衰老过程,如不完全的线粒体脂肪酸氧化。代谢组学的应用将增加我们对衰老网络的理解,并可能有助于发现有助于增强健康衰老的方法。