代謝體學在老化及運動介入研究中之應用

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Title:	代謝體學在老化及運動介入研究中之應用
Other Titles:	Application of Metabonomics in the Study Aging and Exercise Intervention
Authors:	林万登,謝錦城,黃志揚 Lin, Wan-Teng;Huang, Chih-Yang;Hsieh, C. City
Contributors:	行政院國家科學委員會東海大學餐旅管理系
Keywords:	代謝體學；老化；規律運動訓練；生物標記；最小區塊判別分析法 Metabonomics； Aging； Regular exercise training； Biomarkers； Partial least-squares–discriminant analysis (PLS-DA)
Date:	2010
Issue Date:	2012-04-27T03:07:04Z (UTC)
Abstract:	代謝體學在?化及運動介入研究中之應用代謝體學包括特定目標與全面性代謝產物的圖譜分析策?，是一項針對小分子代謝物進?系統性且廣泛的研究工具，對象涵蓋生物體液(如血液、?液或腦脊液)以及生物組織檢體。對於病?、生?性的?激或是基因變?時，代謝體學也被應用於偵測生物系統中多項代謝反應?徑之變化。小分子代謝物是生物系統內最終的生化產物，因此研究這些內生性組成分含?的變化情形可以用?檢測生化反應?徑的整體表現。高齡化是全球各國所面?的重要議題，根據世界衛生組織報告在今後 20-30 ?內，?化人口將在已開發與發展中國家急速增加。面對急速攀升的?化人口，世界各國提高注意並著重於研究?化形成的機制以及延緩?化的對策。?化與生?學和病?學相關，是一種緩慢、漸進且受到多項基因或環境因子交互作用影響而被動的變化過程。許多???如：氧化性傷害、?線體變?、氧化修飾後蛋白羰基的毒性作用以及自由基??已經被用?瞭解造成自然?化各種現象形成的機制。研究內生性代謝物分佈之變化可被預期應用在提供新觀點於?化研究工作上，它將有助於瞭解?化發展過程中新的病?或生?特徵。運動也是調控生化代謝反應的主要因子之一。近??，許多運動科學研究顯示對?同?型運動以及運動表現方面之代謝性與生?性反應感到興趣。運動模式會導致生??況?同的影響，主要差?在於?型、強?以及持續時間。而?化會導致人體肌耐?能?下?，規?的體能活動?僅有增強抗氧化能?與改善心肺功能而且可以預防?人跌倒?的發生與?動失能以節?龐大的醫?資源。我們最近發表的研究結果顯示，以氣相層析質譜(GC/MS) 為主的代謝產物成分分析技術是一種很有效的工具，可用?探討?同運動模式下所造成的生??態變化情形。本研究將應用GC-MS 代謝體學分析平台?研究12 週運動訓?模式下，針對D-半乳?誘發?化動物模型以及?同?齡層?鼠(?輕、中?、?化)，?分析其血漿、?液以及骨骼肌等生物檢體中具潛?的生物標記。同時也針對骨骼肌檢測?項重要生化項目包括以西方點墨法偵測cytochrome C、Bcl-2、Bax、caspase-3、caspase-9、caspase-8、Apaf-1、AIF、PARP，與MAPK 訊息傳遞?徑中 JNK、ERK 與p38 蛋白質表現，並進?組織?片、mt DNA4834 deletion、8-OHdG DNA damage 及TUNEL 分析，以?解?與運動介入對?同?化鼠齡細胞凋亡之調控?徑。在第一?的研究中，我們將針對規?運動訓?是否可以預防加速?化大鼠模式中生化組成分的變?進?驗證。此分析也將用?進一步探討體內代謝產物於誘發?化動物模式下之可能變化情形。在接續的第二?研究中，我們將測試一項假?，即規?運動訓?模式在自然的?化過程中，能夠預防?化所造成的代謝?徑改變、氧化壓?上升以及死亡?目增加。?同部位生物檢體的代謝產物組成份，將透過GC-MS 進?分析。根據所獲得之成分峰(peak)滯?時間及其質譜等?據，進一步加以比對與鑑定出其化學成分，並進?代謝產物分佈之統計分析。所有?據將採用主要成分分析法(Principal component analysis, PCA)以及最小區塊判別分析法(Partial least squares-discriminant analysis, PLS-DA)將大規模的?據資?進?統計運算而將質譜所測出的成分加以分?與歸納並比較規?運動訓?對於?同?齡層大鼠體內代謝產物之影響。希藉由本實驗之研究結果，能?解?化過程在運動介入及代謝體學之關?性，進而建?運動科學在?化分子生物學之資?庫與新的觀點與假?。 Application of Metabonomics in the Study Aging and Exercise Intervention Metabonomics, including targeted and global metabolite profiling strategies, is the systematic and theoretically comprehensive study of the small molecule metabolites that comprise bodily fluids (e.g., plasma, urine or cerebrospinal fluid) and biological tissues. Metabonomics is also an important technology to measure multiple metabolic responses of living systems to pathophysiological stimuli or genetic modification. Metabolites are the final biological products of living systems, so investigating the alteration in level of these endogenous components can verify the response endpoint of biological matrices. Aging is a global dilemma?over the next 20-30 years, elderly populations will increase in both developed countries and developing nations, according to the World Health Organization. Studying the mechanism of aging, as well as the anti-aging needs of the booming elderly population, is drawing ever-increasing attention worldwide. Relevant to physiology and pathology, aging is generally understood as a slow, gradual and passive process influenced by interplay of multiple genetic and environmental factors. A variety of strategies or theories, such as oxidative damage, mitochondrial mutation, carbonyl toxification and free radical theory, have been used to understand the nature of the mechanisms underlying the phenomenon of senescence. To investigate the changes of endogenous metabolite profiles might be expected to provide new insights into the study of aging and, perhaps, reveal new pathological or physiological characteristics of the aging process. Exercise is one of the major metabolism modulators. Metabolic and physiological responses to different types of exercise and implications for exercise performance studies have increased in interest steadily over the past few decades. The main identifying parameters of exercise are type, intensity, and duration, which cause different effects on physiological status. Aging causes us to lose muscle and lose flexibility. Not only does regular physical activity is generally considered to enhance antioxidant capacity and improve cardiac function also can prevent to reduce the risk of disability due to fall and save huge health resources in elderly population.We have previously shown that gas chromatography/mass spectrometry (GC-MS)–based metabonomic analysis is a promising tool to investigate a pathological status with different exercise programs. In the present study, a GC-MS metabonomic platform will be employed to study a 12-week training protocol and to search for potential biomarkers from plasma, urine and skeletal muscle in D-galactose-induced aging rat model and aging-related rats (2, 6, 18 month-old). Western blot analysis will also perform to examine the modulation of skeletal muscle function in aging process including cytochrome C, Bcl-2, Bax, caspase-3, -8, -9, -8, Apaf-1, AIF, PARP, and MAPKs (JNK, ERK and p38) protein levels, as well as the detection of histopathological examination, mtDNA4834 deletion, 8-OHdG DNA damage and TUNEL assay in skeletal muscle. In the first year study, we examine whether the benefits of regular exercise on the alteration of biochemical compositions in accelerated-aging rats. Also, this exam is undertaken to investigate possible differences in metabolites of indeced aging rats. In the second year study, we tested the hypothesis that a regular exercise training program prevents aging-induced alteration of metabolism and increases of oxidative stress and death during the natural aging process. The metabolite profile of biological samples is investigated on GC-MS. Data further underwent partial least-squares–discriminant analysis (PLS-DA) to compare the effects on metabolites of sedentary control and regular exercise training in aging-related rats. Thus, this study focuses on understanding metabonomics and exercise training in aging process and suggesting that investigation of such metabolic interactions on a global level could provide new insights and generate novel hypotheses regarding exercise modulation effects on aging molecules science.
Relation:	研究編號：NSC99-2410-H029-059-MY2 研究期間：2010-08~ 2011-07
Appears in Collections:	[餐旅管理學系所] 國科會研究報告

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