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

老年白人和黑人肌肉减少症特征代谢组学特征的鉴定

• 批准号: 10403502
• 负责人: HUI SHEN
• 金额: $ 57.32万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10403502
• 关键词: Adopted; Aging; Archives; Biological; Biological Assay; Biological Markers; Black American; Black Populations; Body Composition; Body mass index; Complex; Custom; Databases; Diagnosis; Disease; Dual-Energy X-Ray Absorptiometry; Economic Burden; Elderly; Enrollment; Etiology; Fasting; Fracture; Gait speed; Goals; Hand; Hand Strength; Health; Hospitalization; Impairment; Individual; Intervention; Knowledge; Louisiana; Measures; Metabolic Marker; Metabolic Pathway; Methods; Molecular; Molecular Target; Molecular Weight; Muscle function; Muscular Atrophy; Older Population; Osteoporosis; Outcome; Participant; Pathogenesis; Pathway interactions; Patient Recruitments; Pharmaceutical Preparations; Physical Performance; Physiological; Plasma; Predictive Value; Prevention; Protocols documentation; Quality of life; Race; Research; Risk; Risk Factors; Sample Size; Sampling; Science; Sex Differences; Solid; Specificity; Study Subject; Technology; Testing; Time; Validation; Woman; age-related muscle loss; base; biomarker discovery; caucasian American; cost efficient; data archive; falls; follow-up; frailty; high risk; high risk population; improved; innovation; insight; lean body mass; liquid chromatography mass spectrometry; loss of function; men; metabolomics; mortality; muscle form; muscle strength; novel; racial difference; rapid growth; recruit; reduced muscle mass; sarcopenia; sex; tool; trait; working group

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.

肌肉减少症的特征是与年龄相关的肌肉质量和功能丧失，是一个主要的健康问题 老年人口迅速增长，带来巨大的经济负担。其病因主要是 未知，并且没有批准的药物可用。迫切需要针对以下目标的生物标志物 了解肌肉减少症的机制并改进肌肉减少症的预防、诊断和治疗。最近 肌肉减少症的成熟定义包括肌肉质量低和肌肉功能受损，强调 有必要考虑肌肉减少症的不同生理成分，以获得基本和 全面了解该疾病背后的复杂生物学机制。新兴的 代谢组学技术为生物标志物发现提供了强大的工具。然而，应用程序 肌肉减少症研究中的代谢组学方法相当有限。种族/性别的特殊性和普遍性 与肌肉减少症相关的代谢物从未被研究过。拟议研究的目标是确定新颖的 与老年白人和黑人中多个关键肌肉减少症相关特征相关的代谢组标记/概况 使用基于强大的最先进的液相色谱-质谱 (LC-MS) 技术对两性进行分析 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 广泛的数据档案，可有效招募和检查 800 名老年白人和黑人受试者（≥ 60 岁和 200 每个种族-性别组的受试者）。肌肉减少症相关特征，包括肌肉质量、力量和功能将 使用四肢去脂质量/体重指数比 (ALM/BMI)、握力和平常测量 分别为步态速度。锚定在 LOS 上，我们将招募 300 名受试者作为发现组，另外 300 名受试者 作为验证集。我们将选择 100 名肌少症高风险受试者和 100 名低肌少症风险受试者，定义为 ALM/BMI 和握力值均位于参与者分布的下半部分或上半部分 在LOS档案中，作为测试集。在第 4 年，我们将跟踪第 1 年注册的 100 名参与者，作为 预测集。具体目标是：1) 鉴定与肌肉减少症特征相关的新型代谢物 （包括种族、性别和性状特异性/共有的）使用非目标代谢组学方法与相对 发现集中的量化； 2) 使用相同的方法验证目标 1 中鉴定的性状相关代谢物 验证集中的非目标方法，使用已建立的方法阐明/确认代谢物的身份 工作流程，并开发具有绝对定量的靶向 LC-MS 检测，以便在两个方面进行进一步验证 发现和验证集； 3) 评估已验证代谢物在区分受试者中的功效 测试集中肌肉减少症风险低的人中的高风险者，并检查他们的预测值 预测集中肌肉减少症相关性状的纵向变化。凭借创新和最先进的 分析策略，该项目将及时且经济高效地提供重要的新型代谢标记物 肌肉减少症风险，并揭示其生物学机制。