Biomarkers and Genetic Factors Related to Sarcopenia in Women

描述（由申请人提供）：低相对骨骼肌质量（SMM）或肌肉减少症显著导致老年人身体功能下降。关于衰老相关的SMM损失的遗传风险因素及其与环境因素的相互作用知之甚少。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。这些相关性需要在更大的前瞻性研究中得到证实，并且每个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。由于身体功能障碍和残疾在老年妇女中比在男子中更普遍，因此了解老年妇女肌肉损失的机制和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妇女低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和SMM丢失率的关联;和2）评估遗传变异在分解代谢炎性细胞因子中的作用（IL-6，IL-1，TNF-α）以及合成代谢生长因子在一个西班牙裔和非西班牙裔白色绝经后妇女的大队列中，研究与SMM相关的胰岛素样生长因子1（IGF 1，生长激素）和SMM丢失率。研究参与者将来自妇女健康倡议观察性研究。所有这些妇女在9年的随访期间都使用双能X线吸收测定法（DXA）重复测量身体成分。他们的SMM将使用该研究小组开发的DXA衍生方法进行评估。将评估整个样本（n = 2800）中选定分解代谢（例如IL-1、IL 6、TNF-α）以及合成代谢（例如IGF-1和GH）因子的遗传变异。生物标志物的分析，包括IL-6，TNF-α，脂联素，C-反应蛋白，IL-1 ra，IL-6sR，TNF R11，酸不稳定亚基JGF-1和IGFBP-3，将在50%的参与者中进行。最终数据分析将使用回归和混合效应模型。本研究在研究设计、生物测定选择和研究人群方面具有独特性和创新性。这项研究的结果将对预防和减少美国老年妇女肌肉减少症相关的不良健康后果产生重大影响。

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.