Biomarkers and Genetic Factors Related to Sarcopenia in Women

与女性少肌症相关的生物标志物和遗传因素

• 批准号: 7496042
• 负责人: Zhao Chen
• 金额: $ 56.24万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7496042
• 关键词: Acids; Age; Aging; Arts; Biological Assay; Biological Markers; Blood specimen; Body Composition; C-reactive protein; Chronic Disease; Collaborations; Condition; Correlation Studies; Data Analyses; Databases; Development; Diet; Disease; Disease regression; Dual-Energy X-Ray Absorptiometry; Elderly; Environmental Risk Factor; Ethnic Origin; Ethnic group; Genetic; Genetic Variation; Growth Factor; Health; Hispanics; Hormonal; Hormones; IGF1 gene; IL6 gene; Impairment; Inflammatory; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Interleukin-1; Interleukin-6; Intervention; Measurement; Measures; Methods; Modeling; Muscle; Not Hispanic or Latino; Observational Study; Older Population; Outcome; Participant; Persons; Physical Function; Physical activity; Play; Population Study; Postmenopause; Prevention; Prospective Studies; Quality of life; Rate; Recommendation; Relative (related person); Research; Research Design; Research Personnel; Resources; Risk; Roentgen Rays; Role; Sample Size; Sampling; Scanning; Skeletal Muscle; Somatotropin; Specimen; TNF gene; Techniques; Testing; Tumor Necrosis Factor-alpha; United States; Woman; Women' s Health; adiponectin; age related; anakinra; cohort; cost; cytokine; disability; experience; follow-up; genetic analysis; genetic risk factor; genetic variant; human TNF protein; innovation; men; new technology; normal aging; older women; prevent; programs; sarcopenia

DESCRIPTION (provided by applicant): Low relative skeletal muscle mass (SMM) or sarcopenia significantly contributes to the decline in physical functioning among the elderly. Very little is known about genetic risk factors and their interactions with environmental factors in aging-related SMM loss. There are some indications that inflammatory factors and reduced levels of anabolic hormones are associated with lower muscle mass. These associations need to be confirmed in larger prospective studies and the exact role of each identified biomarker in the development of sarcopenia remains to be investigated. Since physical function impairment and disability are more prevalent in women than in men during later life, it is especially important to understand the mechanisms of muscle loss and to prevent sarcopenia among older women. The primary objective of this study is to identify genetic factors and biomarkers that are relevant to low SMM and high rates of SMM loss in older women. We will achieve two specific aims: 1) assess the association of cytokines and hormonal factors with low SMM and the rate of SMM loss; and 2) evaluate the role of genetic variation in catabolic inflammatory cytokines (IL-6, IL-1, TNF-alpha) as well as in anabolic growth factors (IGF1, Growth Hormone) related to SMM and the rate of SMM loss in a large cohort of Hispanic and non-Hispanic White postmenopausal women. Study participants will come from the Women's Health Initiative Observational Study. All of these women have had repeat body composition measurements by using Dual-energy X-ray Absorptiometry (DXA) during the nine- year follow-up. Their SMM will be assessed using a DXA-derived method developed by this research team. Genetic variations in selected catabolic (e.g.IL-1, IL6, TNF-a) as well as anabolic (e.g. IGF-1, and GH) factors will be assessed for the entire sample (n = 2800). Analyses of biomarkers, including IL-6, TNF-a, adiponectin, C-reactive protein, IL-1ra, IL-6sR, TNF Rll, acid labile subunitJGF-1, and IGFBP-3, will be conducted among 50 percent of the participants in this study. Regression and mixed effects models will be used in the final data analysis. This study is unique and innovative in the study design, selection of bioassays, and the study population. Results of this study will have significant impacts on the prevention and reduction of adverse health outcomes associated with sarcopenia of older women in the United States.

描述（由申请人提供）：相对骨骼肌质量（SMM）较低或肌肉减少症会显着导致老年人身体机能下降。对于与衰老相关的 SMM 丧失中的遗传风险因素及其与环境因素的相互作用，人们知之甚少。有一些迹象表明炎症因子和合成代谢激素水平降低与肌肉质量降低有关。这些关联需要在更大规模的前瞻性研究中得到证实，并且每个已确定的生物标志物在肌肉减少症发展中的确切作用仍有待研究。由于女性在晚年身体功能受损和残疾的情况比男性更普遍，因此了解老年女性肌肉损失的机制并预防肌肉减少症尤为重要。本研究的主要目的是确定与老年女性低 SMM 和高 SMM 丢失率相关的遗传因素和生物标志物。我们将实现两个具体目标：1）评估细胞因子和激素因子与低SMM以及SMM损失率的关联； 2) 评估遗传变异在与 SMM 相关的分解代谢炎症细胞因子（IL-6、IL-1、TNF-α）以及合成代谢生长因子（IGF1、生长激素）中的作用，以及 SMM 损失率一大群西班牙裔和非西班牙裔白人绝经后妇女。研究参与者将来自妇女健康倡议观察研究。在九年的随访期间，所有这些女性都使用双能 X 射线吸收测定法 (DXA) 重复进行了身体成分测量。他们的 SMM 将使用该研究团队开发的 DXA 衍生方法进行评估。将评估整个样本 (n = 2800) 中选定的分解代谢（例如 IL-1、IL6、TNF-a）以及合成代谢（例如 IGF-1 和 GH）因子的遗传变异。将在 50% 的受试者中进行生物标志物分析，包括 IL-6、TNF-a、脂联素、C 反应蛋白、IL-1ra、IL-6sR、TNF Rll、酸不稳定亚基 JGF-1 和 IGFBP-3。这项研究的参与者。最终的数据分析将使用回归和混合效应模型。这项研究在研究设计、生物测定方法的选择和研究人群方面都是独特和创新的。这项研究的结果将对预防和减少与美国老年女性肌少症相关的不良健康结果产生重大影响。