Biomarkers and Genetic Factors Related to Sarcopenia in Women

描述(由申请人提供)：相对骨骼肌量(SMM)低或骨骼肌减少是老年人身体功能下降的重要原因。关于遗传风险因素及其与环境因素在衰老相关的SMM丢失中的相互作用，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的降低与肌肉质量下降有关。这些关联需要在更大的前瞻性研究中得到证实，每个已识别的生物标记物在石棺减少症发展中的确切作用仍有待调查。由于晚年女性的身体功能受损和残疾比男性更普遍，因此了解肌肉丧失的机制和预防老年女性的骨质疏松症尤为重要。这项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记物。我们将实现两个具体目标：1)评估细胞因子和激素因素与低SMM和SMM丢失率的关系；2)评估与SMM相关的分解代谢性炎症细胞因子(IL-6、IL-1、TNF-α)和与SMM相关的合成生长因子(IGF1、生长激素)的遗传变异的作用，以及大量西班牙裔和非西班牙裔白人绝经后妇女SMM缺失率。研究参与者将来自妇女健康倡议观察性研究。在九年的随访中，所有这些女性都使用双能X射线吸收测量仪(DXA)重复测量了身体成分。他们的SMM将使用该研究小组开发的DXA衍生方法进行评估。将在整个样本(n=2800)中评估选定的分解代谢因子(如IL-1、IL-6、肿瘤坏死因子-α)以及合成代谢因子(如IGF-1和GH)的遗传变异。本研究将对50%的受试者进行IL-6、肿瘤坏死因子-α、脂联素、C反应蛋白、IL-1ra、IL-6sR、肿瘤坏死因子受体、酸性不稳定亚基JGF-1和IGFBP-3等生物标志物的分析。在最终的数据分析中将使用回归和混合效应模型。本研究在研究设计、生物检测方法的选择和研究人群等方面具有独到之处和创新性。这项研究的结果将对预防和减少与美国老年妇女石棺减少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.