摘要:研究背景:肌少症 (Sarcopenia)是老年醫療照顧中很重要的課題,因為肌少症不僅和老年人的許多慢性疾病以及死亡率有關,還會影響到日常生活活動的功能和生活品質。肌少症的致病機轉是多重原因的。老年人身體組成改變的特徵是脂肪增加同時合併肌肉減少。脂肪組織是活躍的內分泌器官,它會分泌一些脂肪激素(adipokines),不僅在調節胰島素敏感性、葡萄糖和脂質代謝中扮演重要的角色。過去的研究發現肌少症的老年人血中的腫瘤壞死因子-α、介白素-6、和脂締素濃度較高。我們的研究也發現血漿中脂締素和鋅α2糖蛋白和老年衰弱症呈現正相關。過去的研究顯示,骨骼肌系統除了基本的物理收縮功能之外,也參與了內分泌和代謝方面的活動,包括葡萄糖、肝醣和脂質的代謝以及具有免疫的功能。一些肌肉激素(myokines),如鳶尾素(Irisin)、肌聯素(myonectin)、肌肉生長抑制素(myostatin)等是在研究肌少症時很重要的標的。過去幾年的研究顯示骨骼肌和脂肪組織均被視為內分泌的器官,會分泌肌肉激素和脂肪激素。因此,在探討肌少症的致病機轉時應同時考慮骨骼肌及周邊相關組織間的關聯性。也因為肌少症的成因是多元的,很難用單一生物標記來代表。近年來代謝體學的發展,亦有助於應用在代謝性疾病等多重生物標記的分析。研究目的:以老年醫學門診的病人為研究對象,探討肌少症的多重生物標記。同時用實驗室基礎研究方法探討這些生物標記在肌少症致病機轉中的角色。研究方法:我們規劃二年的研究計畫,臨床研究部分以老年醫學門診中肌少症的老人為實驗組,健檢中心的年輕人及健康老年人為對照組,以肌少症的病態生理為基礎分析相關營養素、脂肪激素、肌肉激素、發炎激素及內分泌激素在三組之間的差異。另一方面也將以代謝體學分析方法探尋可能的生物標記。在基礎研究部分,以細胞共同培養為研究模型,探討肌少症致病機轉中肌肉細胞與脂肪細胞之間訊息傳遞及分泌的代謝物之間的交互作用。預期結果:本研究預期可以找到適當的肌少症生物標記,作為評估肌少症的重要參考依據,同時作為早期診斷、早期介入照顧的參考與追蹤。同時了解其致病機轉,可以作為將來營養食品或藥物開發的基礎。
Abstract: Background: Sarcopenia is an important subject in geriatric medical care, since it has been connected to many chronic diseases and the mortality rate among elders. It also affects the function of daily activities and the quality of living. There are multiple factors behind the pathogenesis of sarcopenia, such as age, changes in level of hormones, insufficient nutrients, disuse immobility, degenerating neurons and inflammation. The feature of body composition changes in aged people is the increase of adipose tissue accompanied with the decrease of muscle mass. Adipose tissue is an active endocrine organ, secreting adipokines. These adipokines play some important role in regulating the sensitivity of insulin, glucose and lipid metabolism. There are several studies indicate that there are close relationship between these adipokines and sarcopenia. In elders with sarcopenia, there are elevated plasma levels of TNF-α, IL-6 and adiponectin. In our studies, we found there is a positive correlation between plasma adiponectin level and frailty. We also found a positive correlation between plasma ZAG level and frailty, too. Significantly, it has been shown that the skeletal muscle takes part in, apart from its basic function in physical contractions, endocrine secretion, some immune responses and metabolic activities which include the metabolism of glucose, glycogen and fat. Therefore, the myokines, such as Irisin, myonectin, and myostatin, are important biomarkers for studying sarcopenia. Some path-breaking works during the last decade define skeletal muscle and adipose tissue as endocrine organs releasing myokines and adipokines. Thus one should take the interrelationships between skeletal muscle and its surrounding tissues into the consideration when addressing any questions in the pathogenesis of sarcopenia. Due to its complexity in the pathogenesis of sarcopenia, it is hard for using only one biomarker in representing the progression of sarcopenia. For recent years’ development in the study of metabolomics, this should promote the application of using multi-biomarkers in analyzing the progression of metabolic diseases.Aim: For identifying potential multi-biomarkers in sarcopenia, we analyze the subjects from geriatric out patients department and at the same time studying these biomarkers biochemically in Lab to figure out their roles in the pathogenic mechanism.Methods: We plan for a 2 years’ project. For the clinical study, the experimental group is from sarcopenia subjects of geriatric out patients department and for the control group, subjects are healthy adults and elders from health check-up center. Based on the pathophysiology of sarcopenia, we plan to analyze the difference between adipokines, myokines, cytokines, endocrines and related nutrients among these three groups and also to uncover potential biomarkers using metabolomics analysis. For basic study in Lab, we would like to propose using co-culture of C2C12 and 3T3-L1 cells to discovery the intracellular communication and metabolites secretion between muscle and fat cells to study the pathogenic process of sarcopenia in a more physiological context.Prospectives: 1. To uncover proper biomarkers for sarcopenia. 2. Using these biomarkers as important references for early diagnosis, evaluation and intervention. 3. With the understanding of its pathogenic mechanism, to develop new drugs and nutritional supplement in the future.