Identification of Metabolomic Profiles for Sarcopenia Traits in Older Whites and Blacks

骨质疏松症是一个主要的健康问题，其特征是与年龄相关的肌肉质量和功能的丧失。 随着老龄化老年人口的快速增长，造成了巨大的经济负担。它的病因很大程度上是 未知，并且没有批准的药物可用。迫切需要生物标记物，旨在 了解骨质疏松症的发病机制，提高其预防、诊断和治疗水平。最近 对骨质疏松症的定义包括肌肉重量减少和肌肉功能受损，突出 要获得一个基本和完整的诊断标准，必须考虑骨质疏松症的不同生理成分 全面了解这种疾病背后的复杂生物学机制。新兴市场 代谢组学技术为生物标志物的发现提供了强有力的工具。然而，应用程序 代谢组学方法在骨质疏松症研究中的应用相当有限。种族/性别的特殊性和普遍性 与骨质疏松症相关的代谢物从未被研究过。这项拟议研究的目标是确定小说 老年白人和黑人中与多个与石棺减少相关的关键性状相关的代谢标志物/图谱 使用强大的最先进的液质联用(LC-MS)技术 代谢组学方法。我们将利用我们正在进行的大型路易斯安那州骨质疏松症研究(LOS)及其 广泛的数据归档，可有效地招募和审查800名老年白人和黑人受试者(≥60岁和200岁 每个种族-性别组的受试者)。与骨质疏松症相关的特征，包括肌肉质量、力量和功能 使用阑尾瘦质量/体重指数比率(ALM/BMI)、手握力和通常 步态速度。停靠在洛杉矶，我们将招募300名受试者作为发现集，另外300名受试者 作为验证集。我们将选择100名高风险的LOS受试者和100名低风险的受试者，定义为 ALM/BMI和手握力值在参与者之间的分布的下半部分或上半部分 在洛杉矶档案馆，作为测试集。在第四年，我们会跟进100名在第一年登记为 预测集。其具体目的是：1)确定与石棺减少症特征相关的新代谢物 (包括种族、性别和特征特定/共享的)使用非靶向代谢组学方法与相对 在发现集中进行量化；2)使用相同的 验证集合中的非目标方法，使用已建立的 工作流程，并开发一种具有绝对定量的靶向LC-MS分析，以便在 发现和验证集合；以及3)评估验证代谢物在区分受试者中的能力 在测试集中来自低风险人群的高风险人群，并检查他们的预测价值 预测集合中与石棺减少相关的性状的纵向变化。拥有创新和最先进的 分析策略，该项目将及时和成本效益地提供新的代谢标记，对 骨质疏松症的风险，并揭示其生物学机制。

Sarcopenia, characterized by the age-related loss of muscle mass and function, is a major health problem incurring a huge economic burden with the rapid growth of the aging older population. Its etiology is largely unknown, and no approved medication is available. There is an urgent need for biomarkers aimed at understanding the mechanisms and improving the prevention, diagnosis, and treatment of sarcopenia. Recently developed definitions of sarcopenia include both low muscle mass and impaired muscle function, highlighting the necessity of considering different physiological components of sarcopenia in obtaining a fundamental and comprehensive understanding of the complex biological mechanisms underlying the disorder. The emerging metabolomics technology provides a powerful tool for biomarker discovery. However, applications of the metabolomics approach in sarcopenia research are rather limited. The race/sex specificity and generality of sarcopenia-related metabolites have never been investigated. The Goal of the proposed study is to identify novel metabolomic markers/profiles associated with multiple key sarcopenia-related traits in older whites and blacks of both sexes using a powerful state-of-the-art liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach. We will leverage our large ongoing Louisiana Osteoporosis Study (LOS) and its extensive data archive to efficiently recruit and examine 800 older white and black subjects (≥ 60 years and 200 subjects for each race-sex-group). Sarcopenia-related traits including muscle mass, strength, and function will be measured using the appendicular lean mass/body mass index ratio (ALM/BMI), hand grip strength, and usual gait speed, respectively. Anchored on the LOS, we will enroll 300 subjects as the discovery set and another 300 as the validation set. We will select 100 LOS subjects with high and 100 with low risk for sarcopenia, defined by both ALM/BMI and hand grip strength values in the lower or upper half of the distributions among the participants in the LOS archive, as the testing set. At year 4, we will follow up 100 participants enrolled at year 1 as the prediction set. The Specific Aims are to: 1) identify novel metabolites associated with sarcopenia traits (including race-, sex- and trait-specific/shared ones) using an untargeted metabolomics approach with relative quantification in the discovery set; 2) validate the trait-related metabolites identified in Aim 1 using the same untargeted method in the validation set, elucidate/confirm the identities of metabolites using an established workflow, and develop a targeted LC-MS assay with absolute quantification for further validation in both the discovery and validation sets; and 3) assess the power of the validated metabolites in discriminating subjects with high risk from those with low risk for sarcopenia in the testing set and examine their predictive values for longitudinal changes in sarcopenia-related traits in the prediction set. With the innovative and state-of-the-art analysis strategy, this project will be timely and cost-efficient to provide novel metabolic markers important to sarcopenia risk, and shed lights into its biological mechanisms.